Galaal K, van der Heijden E, Godfrey K, et al.
Adjuvant radiotherapy and/or chemotherapy after surgery for uterine carcinosarcoma.
Cochrane Database Syst Rev. 2013; 2:CD006812 [PubMed]

BACKGROUND: Uterine carcinosarcomas are uncommon with about 35% not confined to the uterus at diagnosis. The survival of women with advanced uterine carcinosarcoma is poor with a pattern of failure indicating greater likelihood of upper abdominal and distant metastatic recurrence.
OBJECTIVES: To evaluate the effectiveness and safety of adjuvant radiotherapy and/or systemic chemotherapy in the management of uterine carcinosarcoma.
SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), 2012, Issue 10, MEDLINE and EMBASE up to November 2012. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.
SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing adjuvant radiotherapy and/or chemotherapy in women with uterine carcinosarcoma.
DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and risk ratios (RRs) comparing adverse events in women who received radiotherapy and/or chemotherapy were pooled in random-effects meta-analyses.
MAIN RESULTS: Three trials met the inclusion criteria and these randomised 579 women, of whom all were assessed at the end of the trials. Two trials assessing 373 participants with stage III to IV persistent or recurrent disease, found that women who received combination therapy had a significantly lower risk of death and disease progression than women who received single agent ifosfamide, after adjustment for performance status (HR = 0.75, 95% confidence interval (CI): 0.60 to 0.94 and HR = 0.72, 95% CI: 0.58 to 0.90 for OS and PFS respectively). There was no statistically significant difference in all reported adverse events, with the exception of nausea and vomiting, where significantly more women experienced these ailments in the combination therapy group than the Ifosamide group (RR = 3.53, 95% CI: 1.33 to 9.37).In one trial there was no statistically significant difference in the risk of death and disease progression in women who received whole body irradiation and chemotherapy, after adjustment for age and FIGO stage (HR = 0.71, 95% CI: 0.48 to 1.05 and HR = 0.79, 95% CI: 0.53 to 1.18 for OS and PFS respectively). There was no statistically significant difference in all reported adverse events, with the exception of haematological and neuropathy morbidities, where significantly less women experienced these morbidities in the whole body irradiation group than the chemotherapy group (RR= 0.02, 95% CI: 0.00 to 0.16) for haematological morbidity and all nine women in the trial experiencing neuropathy morbidity were in the chemotherapy group).
AUTHORS' CONCLUSIONS: In advanced stage metastatic uterine carcinosarcoma as well as recurrent disease adjuvant combination, chemotherapy with ifosfamide should be considered. Combination chemotherapy with ifosfamide and paclitaxel is associated with lower risk of death compared with ifosfamide alone. In addition, radiotherapy to the abdomen is not associated with improved survival.

Hemida R, Goda H, Abdel-Hady el-S, El-Ashry R
Embryonal rhabdomyosarcoma of the female genital tract: 5 years' experience.
J Exp Ther Oncol. 2012; 10(2):135-7 [PubMed]

OBJECTIVES: To present our single institution experience with 10 cases of embryonal rhabdomyosarcoma diagnosed over 5 years.
METHODS: Retrospective analysis of the medical records of 10 patients. The initial presenting data as age, complains and staging were analyzed. Surgical interference of all cases was studied. The follow up data regarding survival and recurrences were analyzed.
RESULTS: The mean age at diagnosis was 4.3 years (range: 2-12). Six cases (60%) were subjected to "True Cut" biopsy and 4 cases (40%) were subjected to complete surgical excision of the tumor. All cases received chemotherapy. "Vincristine, Actinomycin D, Cyclophosphamide" combination was the most commonly used. Radiation therapy was used in 3 patients (30%) in the form of external beam radiation. The 5-year overall survival of our studied cases were 80%.
CONCLUSION: The recurrence rate of our retrospectively studied 10 cases of embryonal rhabdomyosarcoma of vagina and cervix was high (70%). However, five-year survival was 80%. Combined modality treatment is essential to improve prognosis.

Felix AS, Cook LS, Gaudet MM, et al.
The etiology of uterine sarcomas: a pooled analysis of the epidemiology of endometrial cancer consortium.
Br J Cancer. 2013; 108(3):727-34 [PubMed] Article available free on PMC after 19/02/2014

BACKGROUND: Uterine sarcomas are characterised by early age at diagnosis, poor prognosis, and higher incidence among Black compared with White women, but their aetiology is poorly understood. Therefore, we performed a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We also examined risk factor associations for malignant mixed mullerian tumours (MMMTs) and endometrioid endometrial carcinomas (EECs) for comparison purposes.
METHODS: We pooled data on 229 uterine sarcomas, 244 MMMTs, 7623 EEC cases, and 28,829 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with uterine sarcoma, MMMT, and EEC were estimated with polytomous logistic regression. We also examined associations between epidemiological factors and histological subtypes of uterine sarcoma.
RESULTS: Significant risk factors for uterine sarcoma included obesity (body mass index (BMI)≥30 vs BMI<25 kg m(-2) (OR: 1.73, 95% CI: 1.22-2.46), P-trend=0.008) and history of diabetes (OR: 2.33, 95% CI: 1.41-3.83). Older age at menarche was inversely associated with uterine sarcoma risk (≥15 years vs <11 years (OR: 0.70, 95% CI: 0.34-1.44), P-trend: 0.04). BMI was significantly, but less strongly related to uterine sarcomas compared with EECs (OR: 3.03, 95% CI: 2.82-3.26) or MMMTs (OR: 2.25, 95% CI: 1.60-3.15, P-heterogeneity=0.01).
CONCLUSION: In the largest aetiological study of uterine sarcomas, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for EEC. Further exploration of factors that might explain patterns of age- and race-specific incidence rates for uterine sarcoma are needed.

Li RF, Gupta M, McCluggage WG, Ronnett BM
Embryonal rhabdomyosarcoma (botryoid type) of the uterine corpus and cervix in adult women: report of a case series and review of the literature.
Am J Surg Pathol. 2013; 37(3):344-55 [PubMed]

In its classical form, embryonal rhabdomyosarcoma (ERMS, botryoid type) is a vaginal neoplasm occurring in infants and young girls and is often not considered in the differential diagnosis of uterine corpus and cervical spindle cell tumors in adult women. Clinicopathologic and immunohistochemical features of 25 cases of ERMS in women 20 years of age or older were analyzed. Patient age ranged from 20 to 89 years (mean, 44.4 y; median, 46 y), with 8 patients aged 20 to 39 years, 14 patients aged 40 to 59 years, and 3 patients older than 60 years of age. Tumors originated in the cervix in 20 cases and in the uterine corpus in 5. They were characterized by an edematous hypocellular spindle cell proliferation, typically with cellular condensation beneath epithelial surfaces (cambium layer), in which tightly packed hypercellular foci were scattered. Neoplastic cells had hyperchromatic nuclei and minimal cytoplasm, usually with delicate cytoplasmic processes. Occasionally, elongated or globular cells with eosinophilic cytoplasm (rhabdomyoblasts) were evident, but cytoplasmic cross-striations were only rarely identified. Apoptotic bodies and mitotic figures were usually identified in the hypercellular foci. Hemorrhage was common, often making recognition of the hypercellular foci difficult. Desmin and myogenin were coexpressed in 22 of 23 (95.6%) tumors evaluated. Proliferative activity, as assessed by Ki-67 expression, was notably elevated in all tumors evaluated, typically concentrated in the hypercellular foci. Estrogen and progesterone receptors were expressed focally in only 3 of 12 (25%) and 1 of 8 (12.5%) tumors evaluated, respectively. Follow-up was available in 7 cases. Five patients were alive without evidence of disease with follow-up of 3 to 8 years, and 1 patient was alive with disease at 5 months. One patient died at 5 months with pulmonary nodules, but it was not determined whether this was due to metastatic ERMS or the patient's known ductal breast carcinoma. ERMS has a broader clinical profile than classically expected and should be considered in the differential diagnosis of a uterine corpus or cervical spindle cell tumor, regardless of patient age. Recognition can be rendered difficult by the hypocellular background, which can suggest a benign polyp or low-grade tumor, and hemorrhage, which can obscure the characteristic hypercellular foci. Identification of hypercellular foci in which mitotic activity and apoptotic bodies are found, desmin and myogenin are coexpressed, proliferative activity is notably elevated, and hormone receptor expression is usually absent is very useful for establishing the diagnosis.

Carta G, Palermo P, Di Ramio R, et al.
Leiomyosarcoma after hysteroscopic myomectomy: a case report.
Eur J Gynaecol Oncol. 2012; 33(6):656-7 [PubMed]

OBJECTIVES: The aim of this study was to illustrate the importance of hysteroscopy in the evolution of mitotically active leiomyoma to leiomyosarcoma (LMS). Uterine sarcomas are rare tumors. The three microscopic criteria are: 1) the presence of coagulative tumor necrosis, 2) high mitotic index (exceeding 15 x 10 catabolite gene activator (CGA) and 3) occurrence of moderate to severe cytologic atypia. The authors report a case of a 52-year-old nulliparous woman with a LMS detected two months after a hysteroscopic resection of a mitotically active leiomyoma. After the first hysteroscopic resection the diagnosis was atypical leiomyoma with a mitotic index of two per ten high-power field (hpf) in the absence of coagulation necrosis. After two months, a new myoma was detected and another hysteroscopic resection was performed: the microscopic diagnosis was LMS and a total abdominal hysterectomy with bilateral salpingo-oophorectomy (BSO) was performed.
CONCLUSION: The patient must undergo close clinical and instrumental follow-up procedures. Hysteroscopy plays an important role in the evaluation and evolution of both recurrent and de novo disease.

Capobianco G, Pili F, Contini M, et al.
Analysis of epidermal growth factor receptor (EGFR) status in endometrial stromal sarcoma.
Eur J Gynaecol Oncol. 2012; 33(6):629-32 [PubMed]

PURPOSE: Endometrial stromal sarcomas (ESSs) are rare neoplasms, which are currently treated by surgery, whereas effective adjuvant therapies have not yet been established. Recently, epidermal growth factor receptor (EGFR) expression has been described in ESS, and a potential role of EGFR-targeted adjuvant therapies has been proposed. The aim of this study was to analyze EGFR status in an ESS series and to evaluate their potential role as molecular targets.
MATERIALS AND METHODS: EGFR status was investigated in a total of ten cases of ESS, which included seven low-grade ESS and three undifferentiated ESS cases. EGFR expression levels were assessed by immunohistochemistry, and gene amplification analysis was performed with dual-color fluorescence in situ hybridization (FISH).
RESULTS: Nine out of ten ESS cases showed positive immunostaining, whereas FISH analysis demonstrated constantly negative results.
CONCLUSIONS: This study confirmed that EGFR is frequently overexpressed in ESS. FISH analysis did not show EGFR amplification in any of the tumors, therefore EGFR expression in ESS should be related to different genetic mechanisms.

Tanner EJ, Toussaint T, Leitao MM, et al.
Management of uterine adenosarcomas with and without sarcomatous overgrowth.
Gynecol Oncol. 2013; 129(1):140-4 [PubMed]

OBJECTIVES: Uterine adenosarcomas (AS) are rare tumors composed of malignant stromal and benign epithelial components. We sought to evaluate the role of primary surgery, adjuvant treatments, and salvage therapies for patients with uterine adenosarcomas.
METHODS: We identified all patients diagnosed with AS from 1990 to 2009 at our institution. Patient demographics, surgical procedures, sites of metastatic disease, and histologic features (e.g., presence of sarcomatous overgrowth, and heterologous elements) were collected. Treatment regimens and survival outcomes were evaluated.
RESULTS: Thirty-one patients were evaluable for this study: 19 (61%) received up-front treatment at our institution and 12 (39%) received treatment for recurrent disease. Most of the up-front treated patients (15, 79%) were diagnosed with stage I disease and underwent hysterectomy (100%) with bilateral salpingo-oophorectomy (84%). Of the 19 patients treated at our institution from time of initial diagnosis, 5 (26%) patients recurred (median follow-up, 72.9 months; range, 3-154). In 5 patients with sarcomatous overgrowth (AS+SO), the 2-year progression-free and overall survival rates were both 20% versus 100% for 14 patients without sarcomatous overgrowth. Responses to systemic treatment of measurable disease were observed in patients with and without sarcomatous overgrowth, but no optimal treatment strategy could be identified for either groups.
CONCLUSIONS: Unlike AS without sarcomatous overgrowth, AS+SO is an aggressive disease with a high recurrence rate. In our series, no optimal adjuvant or systemic treatment strategy was identifiable but standard sarcoma chemotherapy regimens appear to have efficacy in both AS and AS+SO.

Cate F, Bridge JA, Crispens MA, et al.
Composite uterine neoplasm with embryonal rhabdomyosarcoma and primitive neuroectodermal tumor components: rhabdomyosarcoma with divergent differentiation, variant of primitive neuroectodermal tumor, or unique entity?
Hum Pathol. 2013; 44(4):656-63 [PubMed]

Three cases of composite uterine neoplasms comprised of primitive neuroectodermal tumor (PNET) and rhabdomyosarcoma (RMS) have previously been described, including only one wherein the rhabdomyosarcomatous component was of the embryonal subtype. Whether such composite neoplasms are a variant of RMS, a variant of PNET, or a unique entity is unknown. We report the clinicopathologic, immunohistochemical, and molecular cytogenetic findings in a case of uterine embryonal RMS with coexisting PNET that was diagnosed in a 25-year-old female. The tumor broadly involved the cervix and corpus uteri and resulted in uterine inversion. The 2 distinct components each showed classic morphologic features, including cartilage in the RMS component. The unique combination of histologic, immunohistochemical and molecular findings in composite neoplasms of this type raises a question of whether they should be classified and treated as RMS, PNET, or a unique high-grade sarcoma. A variety of clinicopathologic arguments are presented that support the notion that the current neoplasm is an embryonal rhabdomyosarcoma with divergent neuroectodermal and cartilaginous differentiation.

D'Angelo E, Ali RH, Espinosa I, et al.
Endometrial stromal sarcomas with sex cord differentiation are associated with PHF1 rearrangement.
Am J Surg Pathol. 2013; 37(4):514-21 [PubMed]

Endometrial stromal tumors may pose diagnostic challenges particularly when they exhibit variant histologic appearances, involve extrauterine sites, or present as metastatic disease. In such cases, use of immunohistochemical markers and identification of specific nonrandom chromosomal rearrangements may be helpful. Over the last decade, fluorescence in situ hybridization (FISH) has been progressively incorporated as a diagnostic tool for the evaluation of endometrial stromal tumors. The purpose of this study was to review a series of these tumors and compare the results of FISH analysis with the clinicopathologic characteristics. Three endometrial stromal nodules (ESNs), 13 endometrial stromal sarcomas (ESSs), and 7 undifferentiated endometrial sarcomas (UESs) were reviewed. Three metastases from 1 of the ESS cases were also analyzed. Nine of these tumors (1 ESN, 8 ESSs, and 1 UES) exhibited unusual histologic features, including smooth muscle (3), sex cord (7), epithelioid (1), fibromyxoid (1), and skeletal muscle (2) differentiation. A tissue microarray was prepared, and FISH analysis was performed using break-apart and fusion probes for JAZF1, SUZ12, EPC1, and PHF1 genes. FISH was successful in 22 cases, and rearrangements involving JAZF1, SUZ12, EPC1, and PHF1 genes were detected in 10 of the 22 (45%) uterine tumors, including 2 of the 3 ESNs and 8 of 12 ESSs. Genetic rearrangements were found neither in the 3 metastases of the ESS nor in any of the UESs. It is noteworthy that a correlation between sex cord differentiation and PHF1 rearrangement was encountered in ESSs (P=0.008). In our series, all ESSs showing sex cords had PHF1 genetic rearrangement, suggesting that such rearrangements may induce sex cord differentiation.

Seidman MA, Oduyebo T, Muto MG, et al.
Peritoneal dissemination complicating morcellation of uterine mesenchymal neoplasms.
PLoS One. 2012; 7(11):e50058 [PubMed] Article available free on PMC after 19/02/2014

BACKGROUND: Power morcellation has become a common technique for the minimally invasive resection of uterine leiomyomas. This technique is associated with dissemination of cellular material throughout the peritoneum. When morcellated uterine tumors are unexpectedly found to be leiomyosarcomas or tumors with atypical features (atypical leiomyoma, smooth muscle tumor of uncertain malignant potential), there may be significant clinical consequences. This study was undertaken to determine the frequency and clinical consequence of intraperitoneal dissemination of these neoplasms.
METHODOLOGY/PRINCIPAL FINDINGS: From 2005-2010, 1091 instances of uterine morcellation were identified at BWH. Unexpected diagnoses of leiomyoma variants or atypical and malignant smooth muscle tumors occurred in 1.2% of cases using power morcellation for uterine masses clinically presumed to be "fibroids" over this period, including one endometrial stromal sarcoma (ESS), one cellular leiomyoma (CL), six atypical leiomyomas (AL), three smooth muscle tumor of uncertain malignant potential (STUMPs), and one leiomyosarcoma (LMS). The rate of unexpected sarcoma after the laparoscopic morcellation procedure was 0.09%, 9-fold higher than the rate currently quoted to patients during pre-procedure briefing, and this rate may increase over time as diagnostically challenging or under-sampled tumors manifest their biological potential. Furthermore, when examining follow-up laparoscopies, both from in-house and consultation cases, disseminated disease occurred in 64.3% of all tumors (zero of one ESS, one of one CL, zero of one AL, four of four STUMPs, and four of seven LMS). Only disseminated leiomyosarcoma, however, was associated with mortality. Procedures are proposed for pathologic evaluation of morcellation specimens and associated follow-up specimens.
CONCLUSIONS/SIGNIFICANCE: While additional study is warranted, these data suggest uterine morcellation carries a risk of disseminating unexpected malignancy with apparent associated increase in mortality much higher than appreciated currently.

Davidson B, Abeler VM, Hellesylt E, et al.
Gene expression signatures differentiate uterine endometrial stromal sarcoma from leiomyosarcoma.
Gynecol Oncol. 2013; 128(2):349-55 [PubMed]

OBJECTIVE: Endometrial stromal sarcoma (ESS) and leiomyosarcoma (LMS) are the two most common uterine sarcomas, but both are rare tumors. The aim of the present study was to compare the global gene expression patterns of ESS and LMS.
METHODS: Gene expression profiles of 7 ESS and 13 LMS were analyzed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry.
RESULTS: Unsupervised hierarchical clustering using all 54,675 genes in the array separated ESS from LMS samples. We identified 549 unique probes that were significantly differentially expressed in the two malignancies by greater than 2-fold with 1% FDR cutoff using one-way ANOVA with Benjamini-Hochberg correction, of which 336 and 213 were overexpressed in ESS and LMS, respectively. Genes overexpressed in ESS included SLC7A10, EFNB3, CCND2, ECEL1, ITM2A, NPW, PLAG1 and GCGR. Genes overexpressed in LMS included CDKN2A, FABP3, TAGLN, JPH2, GEM, NAV2 and RAB23. The top 100 genes overexpressed in LMS included those coding for myosin light chain and caldesmon, but not the genes coding for desmin or actin. CD10 was not overexpressed in ESS. Results for selected genes were validated by quantitative real-time PCR and immunohistochemistry.
CONCLUSIONS: We present the first study in which gene expression profiling was shown to distinguish between ESS and LMS. The molecular signatures unique to each of these malignancies may aid in expanding the diagnostic battery for their differentiation, and may provide a molecular basis for prognostic studies and therapeutic target discovery.

Lim D, Wang WL, Lee CH, et al.
Old versus new FIGO staging systems in predicting overall survival in patients with uterine leiomyosarcoma: a study of 86 cases.
Gynecol Oncol. 2013; 128(2):322-6 [PubMed]

OBJECTIVES: Uterine leiomyosarcoma (uLMS) was staged using the FIGO system for endometrial cancers. The new FIGO system takes into consideration tumor size disregarding myometrial and cervical involvement. We aimed to compare the two systems and see which more accurately predicts overall survival (OS).
METHODS: 86 patients with uLMS (1984-2010) were retrospectively staged using both FIGO systems. Mean OS rates were estimated using the Kaplan-Meier method.
RESULTS: More patients had stage-I disease by the new FIGO system (42 versus 33). Five versus 18 and 27 versus 5 had old and new stage-II and III diseases respectively. Five and 4 patients with old stage II and III uLMS respectively were downstaged to stage I while 18 with old stage III were downstaged to stage II. Median follow-up was 23.5 months with a median OS of 114 (95% CI, 61-166) months. Although patients with stage I tumors had a higher mean OS rate compared to those with higher stage disease by either system, patients with old stage II-IV disease showed similar mean OS rates, with stage III-IV patients having a slightly better mean OS and a similar trend was observed with the new system. Patients with new FIGO stage III had a higher mean OS rate than those with stage II or IV disease (37.6 versus 28.1 and 34.3 months). Nonetheless, no statistical significant differences were seen in OS according to stage using either system (p=0.786 and p=0.400 respectively).
CONCLUSION: Neither FIGO staging system is ideal in classifying patients into four clinically significant stages.

Kämpjärvi K, Mäkinen N, Kilpivaara O, et al.
Somatic MED12 mutations in uterine leiomyosarcoma and colorectal cancer.
Br J Cancer. 2012; 107(10):1761-5 [PubMed] Article available free on PMC after 06/11/2013

BACKGROUND: Mediator complex participates in transcriptional regulation by connecting regulatory DNA sequences to the RNA polymerase II initiation complex. Recently, we discovered through exome sequencing that as many as 70% of uterine leiomyomas harbour specific mutations in exon 2 of mediator complex subunit 12 (MED12). In this work, we examined the role of MED12 exon 2 mutations in other tumour types.
METHODS: The frequency of MED12 exon 2 mutations was analysed in altogether 1158 tumours by direct sequencing. The tumour spectrum included mesenchymal tumours (extrauterine leiomyomas, endometrial polyps, lipomas, uterine leiomyosarcomas, other sarcomas, gastro-intestinal stromal tumours), hormone-dependent tumours (breast and ovarian cancers), haematological malignancies (acute myeloid leukaemias, acute lymphoid leukaemias, myeloproliferative neoplasms), and tumours associated with abnormal Wnt-signalling (colorectal cancers (CRC)).
RESULTS: Five somatic alterations were observed: three in uterine leiomyosarcomas (3/41, 7%; Gly44Ser, Ala38_Leu39ins7, Glu35_Leu36delinsVal), and two in CRC (2/392, 0.5%; Gly44Cys, Ala67Val).
CONCLUSION: Somatic MED12 exon 2 mutations were observed in uterine leiomyosarcomas, suggesting that a subgroup of these malignant tumours may develop from a leiomyoma precursor. Mutations in CRC samples indicate that MED12 may, albeit rarely, contribute to CRC tumorigenesis.

Birkeland E, Wik E, Mjøs S, et al.
KRAS gene amplification and overexpression but not mutation associates with aggressive and metastatic endometrial cancer.
Br J Cancer. 2012; 107(12):1997-2004 [PubMed] Article available free on PMC after 04/12/2013

BACKGROUND: Three quarter of endometrial carcinomas are treated at early stage. Still, 15 to 20% of these patients experience recurrence, with little effect from systemic therapies. Homo sapiens v-Ki-ras2 Kirsten rat sarcoma viral oncogenes homologue (KRAS) mutations have been reported to have an important role in tumorigenesis for human cancers, but there is limited knowledge regarding clinical relevance of KRAS status in endometrial carcinomas.
METHODS: We have performed a comprehensive and integrated characterisation of genome-wide expression related to KRAS mutations and copy-number alterations in primary- and metastatic endometrial carcinoma lesions in relation to clinical and histopathological data. A primary investigation set and clinical validation set was applied, consisting of 414 primary tumours and 61 metastatic lesions totally.
RESULTS: Amplification and gain of KRAS present in 3% of the primary lesions and 18% of metastatic lesions correlated significantly with poor outcome, high International Federation of Gynaecology and Obstetrics stage, non-endometrioid subtype, high grade, aneuploidy, receptor loss and high KRAS mRNA levels, also found to be associated with aggressive phenotype. In contrast, KRAS mutations were present in 14.7% of primary lesions with no increase in metastatic lesions, and did not influence outcome, but was significantly associated with endometrioid subtype, low grade and obesity.
CONCLUSION: These results support that KRAS amplification and KRAS mRNA expression, both increasing from primary to metastatic lesions, are relevant for endometrial carcinoma disease progression.

Fadare O, Khabele D
Salpingo-oophorectomy specimens for endometrial cancer staging: a comparative analysis of representative sampling versus whole tissue processing.
Hum Pathol. 2013; 44(4):643-50 [PubMed]

Involvement of the ovary and/or fallopian tube by an endometrial cancer is uncommon but clinically significant because this is one of the indications for adjuvant chemotherapy. The authors evaluated whether the routine microscopic evaluation of the adnexal organs in this setting should be of the entire specimen or of representative sections. Slides and reports were reviewed for 105 consecutive patients who underwent a staging salpingo-oophorectomy (205 ovaries, 210 tubes) for endometrial carcinoma/carcinosarcoma. The study period encompassed the periods before and after an institutional policy change from discretionary (predominantly representative) adnexal sampling to obligatory total processing. Ninety-four and 111 ovaries (and 92 and 118 tubes) were entirely and representatively processed, respectively. Even when using the most expansive definition of ovarian gross abnormality (definition with the highest sensitivity and lowest specificity for microscopically confirmed cancer), we still identified 4 (of 148; 2.7%) grossly normal ovaries and 3 (of 187; 1.6%) grossly normal tubes that were found to harbor microscopic cancers. There was no significant increase in the number of grossly occult cancers detected after the policy change, and 5 (71%) of the 7 grossly occult cancers were in the representatively sampled group. Approximately 3.76 more blocks per patient were required for total overrepresentative processing, and the total cost of these additional sections was estimated to be $25.57 per patient. In conclusion, the 1.6% to 2.7% of grossly normal adnexa that proved to be cancerous represents, at least theoretically, the risk for misdiagnosis and understaging that is associated with representative sampling, at relatively modest savings. However, the findings in this study do not provide direct evidentiary support for routine complete processing.

Cordero García JM, López de la Manzanara Cano CA, García Vicente AM, et al.
Study of the sentinel node in endometrial cancer at early stages: preliminary results.
Rev Esp Med Nucl Imagen Mol. 2012; 31(5):243-8 [PubMed]

AIM: To investigate the applicability of the sentinel lymph node biopsy technique in early stages of endometrial cancer.
MATERIAL AND METHODS: A prospective study that included consecutive patients with a histological diagnosis of clinical state I endometrial carcinoma was performed. Two doses of 2 mCi (74 MBq) of (99m)Tc-albumin nanocolloid were injected in the uterine cervix, and planar and SPECT-CT images were obtained at one hour, and at 24 hours if no migration of the tracer was observed. Methylene blue dye was also injected into the cervix immediately prior to the surgery. A gamma probe was used during the surgical procedure for sentinel lymph node identification. In all cases, a hysterectomy, double adnexectomy and pelvic lymphadenectomy were performed, carrying out a histological analysis (hematoxylin-eosin) of the sentinel lymph nodes and the lymphadenectomy specimen.
RESULTS: We included 19 patients, with a final diagnoses of endometrioid carcinoma (18 cases) and endometrial stromal sarcoma (1 case). At least one sentinel lymph node was identified in 17 of them (89.5% detection rate). Twenty-nine sentinel lymph nodes were identified during surgery, all of them negative for neoplastic infiltration. No metastatic invasion was found in the pelvic lymphadenectomy specimens as well.
CONCLUSIONS: The sentinel lymph node biopsy technique seems to be a reliable tool in nodal staging of endometrial cancer at early stages, with an acceptable detection rate and high histological correlation. The low prevalence of lymphatic spread in this group of patients and the encouraging results obtained could make the sentinel lymph node an alternative to routine complete lymphadenectomy.

Sah SP, McCluggage WG
DOG1 immunoreactivity in uterine leiomyosarcomas.
J Clin Pathol. 2013; 66(1):40-3 [PubMed]

AIMS: DOG1 is a recently described marker of gastrointestinal stromal tumour (GIST) which is considered to be extremely sensitive and, among mesenchymal neoplasms, quite specific for this tumour type. Following the identification of DOG1 immunoreactivity in a uterine leiomyosarcoma, we wished to ascertain how prevalent DOG1 immunoreactivity was in this tumour type.
METHODS: We stained a series of uterine leiomyosarcomas (n=26) with DOG1 and with CD117 (c-kit), another marker of GIST. Staining with both markers was classified as negative, focal (<50% tumour cells positive) or diffuse (≥50% tumour cells positive).
RESULTS: DOG1 immunoreactivity was present in seven of 26 (27%) leiomyosarcomas. Staining was focal in five cases and diffuse in two. CD117 was positive in three of 26 (11.5%) cases, two focal and one diffuse. Two cases were positive with DOG1 and CD117. One of five uterine leiomyomas was focally positive with DOG1, and one extrauterine pelvic leiomyoma was diffusely positive with this marker.
CONCLUSIONS: Since GISTs have rarely been described as primary uterine neoplasms, the presence of DOG1 immunoreactivity in a uterine leiomyosarcoma may result in diagnostic confusion, and a panel of markers is necessary for diagnosis. Uterine leiomyosarcomas should be added to the list of mesenchymal neoplasms which may be DOG1 positive.

Angelini A, Di Pietro R, Centurione L, et al.
Inhibition of P-glycoprotein-mediated transport by S-adenosylmethionine and cynarin in multidrug-resistant human uterine sarcoma MES-SA/Dx5 cells.
J Biol Regul Homeost Agents. 2012 Jul-Sep; 26(3):495-504 [PubMed]

Multidrug resistance (MDR) to anticancer chemotherapy is often mediated by the overexpression of the plasma membrane drug transporter P-glycoprotein (Pgp) encoded by multidrug resistance gene (MDR1). Various chemosensitizing agents are able to inhibit Pgp activity but their clinical application is limited by their toxicity. Furthermore, hepatotoxicity related to chemotherapy causes delays of treatment in cancer patients and often requires supplementation of anti-tumour therapy with hepatoprotective agents. In this in vitro study, we investigated the effectiveness of an endogenous hepatoprotective agent, S-adenosylmethionine (SAMe), and a natural hepatoprotective compound, Cynarin (Cyn), to inhibit Pgp activity in order to evaluate their potential use as chemosensitizing agents. Human doxorubicin (doxo) resistant uterine sarcoma cells (MES-SA/Dx5) expressing high levels of Pgp were treated with two hepatoprotectors at various concentrations (1, 5 and 10 microM) that are clinically achievable, in the presence or absence of three different concentrations of doxo (2, 4 and 8 microM). In order to evaluate the effects of both hepatoprotectors, we measured the intracellular accumulation and cytotoxicity of doxo, the cellular GSH level, ROS production and catalase (CAT) activity. We found that treatment with 2, 4 and 8 microM doxo in the presence of SAMe or Cyn significantly increased the doxo accumulation and cytotoxicity on MES-SA/Dx5 cells, when compared to control cells receiving doxo alone. Moreover, treatment with SAMe or Cyn significantly increased GSH content, greater than 80 percent and 60 percent, respectively) and CAT activity greater than 60 and 150 percent, respectively) in resistant cancer cells, while ROS production was below the values of corresponding untreated control cells. Our in vitro findings provide a rationale for the potential clinical use of these hepatoprotectors both as chemosensitizing agents, to reverse Pgp-mediated MDR, and as antioxidants to protect normal cells from chemotherapy-induced cytotoxixity.

Reichardt P
The treatment of uterine sarcomas.
Ann Oncol. 2012; 23 Suppl 10:x151-7 [PubMed]

Uterine sarcomas are rare and comprise only 3% of all uterine cancers. Within the group of adult soft tissue sarcomas, they account for ∼7% of new cases. They consist of several distinct histological subtypes like leiomyosarcoma, endometrial stromal tumors, undifferentiated sarcomas, pure heterologous sarcomas, and mixed epithelial and mesenchymal tumors. Standard treatment in localized disease is abdominal hysterectomy. Bilateral salpingo-oophorectomy and lymphadenectomy have no proven value in leiomyosarcomas and high-grade undifferentiated sarcomas. However, in endometrial stromal tumors, given the hormonal reponsiveness of most tumors, salpingo-oophorectomy is generally recommended. Carcinosarcomas are treated according to current recommendations for epithelial uterine cancers. In leiomyosarcomas, postoperative radiation does not improve both relapse-free and overall survival. adjuvant chemotherapy seems to improve survival in the context of uncontrolled phase II trials. However, it is currently not considered standard of care in the absence of data from randomized trials. In contrast, adjuvant chemotherapy does improve overall survival in carcinosarcomas and is therefore considered standard of care. Systemic therapy for advanced uterine leiomyosarcomas, undifferentiated uterine sarcomas, and heterologous sarcomas is generally following the recommendations for adult soft tissue sarcomas. Endometrial stromal sarcomas are usually hormonal receptor positive, which allows endocrine therapy in most cases.

Rahman MT, Nakayama K, Ishikawa M, et al.
NAC1, a BTB/POZ protein overexpressed in uterine sarcomas.
Anticancer Res. 2012; 32(9):3841-5 [PubMed]

BACKGROUND: The purpose of this study was to investigate the role of Nucleus accumbens-associated 1 (NAC1) in the development of uterine sarcomas.
MATERIALS AND METHODS: NAC1 expression and localization in the normal myometrium, benign leiomyoma, and uterine sarcoma were assessed with immunohistochemistry. NAC1-specific siRNA was used to inactivate NAC1 for in vitro biological assays.
RESULTS: Almost all cases of uterine sarcoma were found to overexpress NAC1. Expression of NAC1 was significantly higher in uterine sarcomas than in benign leiomyomas (p<0.0001). NAC1 gene knockdown inhibited cell growth and induced apoptosis in SKN, a leiomyosarcoma cell line, and in OMC-9, an endometrial stromal sarcoma cell line, both of which overexpress NAC1.
CONCLUSION: Uterine sarcomas with NAC1 overexpression are clinically the most aggressive, chemoresistant, and radioresistant tumors. Therefore, detection of NAC1 overexpression in uterine sarcomas may identify patients who will benefit from NAC1-targeted therapy.

Hibino M, Akazawa K, Hikino K, Oe M
Pulmonary tumor embolism secondary to uterine corpus carcinosarcoma mimicking pulmonary thromboembolism.
Intern Med. 2012; 51(18):2603-7 [PubMed]

We herein report a case of pulmonary tumor embolism caused by hematogenous metastasis that mimicked pulmonary thromboembolism in a 62-year-old Japanese woman with a history of uterine corpus carcinosarcoma. The case suggests that tumor embolism must be included in the differential diagnoses of respiratory symptoms in patients with a history of malignancy. It also illustrates the usefulness of such findings as beaded, dilated pulmonary arteries by computed tomography (CT) and high (18)F-fluorodeoxyglucose (FDG) uptake by fusion FDG positron emission tomography/CT imaging for differentiating a pulmonary tumor embolism from pulmonary thromboembolism.

Lee CH, Ali RH, Rouzbahman M, et al.
Cyclin D1 as a diagnostic immunomarker for endometrial stromal sarcoma with YWHAE-FAM22 rearrangement.
Am J Surg Pathol. 2012; 36(10):1562-70 [PubMed] Article available free on PMC after 01/10/2013

Endometrial stromal sarcoma (ESS) characterized by YWHAE-FAM22 genetic fusion is histologically higher grade and clinically more aggressive than ESS with JAZF1-SUZ12 or equivalent genetic rearrangements, hence it is clinically important to recognize this subset of ESS. To identify diagnostic immunomarkers for this biologically defined ESS subset, we compared gene expression profiles between YWHAE-FAM22 ESS and JAZF1-rearranged ESS. These studies showed consistent upregulation of cyclin D1 in YWHAE-FAM22 ESS compared with JAZF1-SUZ12 ESS. Immunohistochemically, the high-grade round cell component of all 12 YWHAE-FAM22 ESS demonstrated diffuse (≥70%) moderate to strong nuclear cyclin D1 staining, and this diffuse positivity was not seen in 34 ESSs with JAZF1 and equivalent genetic rearrangements or in 21 low-grade ESS with no demonstrable genetic rearrangements. In a series of 243 non-ESS pure uterine mesenchymal and mixed epithelial-mesenchymal tumors, only 2 of 8 undifferentiated endometrial sarcomas with nuclear uniformity and 1 of 80 uterine leiomyosarcomas demonstrate diffuse cyclin D1 immunoreactivity. Both cyclin D1-positive undifferentiated endometrial sarcomas showed diffuse strong CD10 staining, which is consistently absent in the high-grade round cell component of YWHAE-FAM22 ESS. The low-grade spindle cell component of YWHAE-FAM22 ESS showed a spatially heterogenous cyclin D1 staining pattern that was weaker and less diffuse overall. Our findings indicate that cyclin D1 is a sensitive and specific diagnostic immunomarker for YWHAE-FAM22 ESS. When evaluating high-grade uterine sarcomas, cyclin D1 can be included in the immunohistochemical panel as an indicator of YWHAE-FAM22 ESS.

Zhang LL, Tang Q, Wang Z, Zhang XS
Alveolar soft part sarcoma of the uterine corpus with pelvic lymph node metastasis: case report and literature review.
Int J Clin Exp Pathol. 2012; 5(7):715-9 [PubMed] Article available free on PMC after 01/10/2013

Alveolar soft part sarcoma (ASPS) is a rare malignant soft tissue tumor, mainly localized in the extremities, occurring principally in adolescents and young adults. ASPS is uncommon in the female genital tract , and only 37 cases have been reported so far, including 9 cases in the uterine corpus and 17 cases in the uterine cervix. We here reported a case of ASPS occurring in the lower uterine segment . The case showed typical histological and immunohistochemical features. The patient had pelvic and para-aortic lymph node metastasis. To the best of our knowledge, it is the first such case described.

Romero-Pérez L, Castilla MÁ, López-García MÁ, et al.
Molecular events in endometrial carcinosarcomas and the role of high mobility group AT-hook 2 in endometrial carcinogenesis.
Hum Pathol. 2013; 44(2):244-54 [PubMed]

The molecular events implicated in the development of endometrial carcinosarcoma remain poorly understood. Using complementary DNA microarrays, we analyzed a group of 15 endometrial carcinosarcomas and compared their gene expression profiles with those obtained from a group of 23 endometrioid endometrial carcinomas. We demonstrated changes in the expression of genes modulating processes such as the epithelial to mesenchymal transition, muscle differentiation, the expression of cancer/testis antigens, and immune response in endometrial carcinosarcomas. The high mobility group AT-hook 2 gene is an embryonic nuclear factor that mediates epithelial to mesenchymal transition in various tumor models, and it was among the genes overexpressed in endometrial carcinosarcomas. High mobility group AT-hook 2 overexpression was confirmed in 54% of endometrial carcinosarcomas by quantitative real time-polymerase chain reaction and immunohistochemistry. Moreover, we found a significant inverse correlation between the expression of high mobility group AT-hook 2 and let-7b, a member of the let-7 family of microRNAs that represses high mobility group AT-hook 2 expression. These changes were also associated with overexpression of Lin28B, a suppressor of microRNA biogenesis that is implicated in cancer progression and metastasis. Finally, high mobility group AT-hook 2 overexpression, which was detected in less than 3% of endometrioid endometrial carcinomas, was observed in many nonendometrioid carcinomas (46% of 28 samples). This pattern of expression, restricted to nonendometrioid carcinomas and endometrial carcinosarcomas, reflects a role for high mobility group AT-hook 2 in endometrial carcinogenesis that is associated with aggressive phenotypes and points to its potential use as a marker to distinguish between endometrioid and nonendometrioid tumors.

Cormier B, Sauthier P, Lussier C, et al.
Determinants of lymph node count in endometrial cancer surgical staging.
Int J Gynecol Cancer. 2012; 22(8):1361-6 [PubMed]

OBJECTIVE: Lymphadenectomy is a fundamental procedure in gynecologic oncology, but there is an ongoing debate concerning its indication in endometrial cancer. Lymph node (LN) count has been used as a surrogate marker for quality of staging in endometrial cancer. Because of variability in reported LN counts in the literature and within our practice, we aimed to better understand the factors that influence the final LN count in endometrial cancer staging.
METHODS: We conducted a retrospective case study of patients with endometrial cancer who underwent surgical staging at our institution between April 1, 2005, and February 3, 2007. Linear regression was used to determine the association between LN count and a series of predictor variables.
RESULTS: Of 131 patients, 100 patients (76%) had stage I disease and 9 patients (7%) had LN metastasis. The mean (SD) LN count was 9.5 (7.8). We found no significant difference in LN count according to age, tumor histology, stage, or surgeon. Lymph node count decreased by 1 for each 5-unit (kg/m(2)) increase in body mass index (coefficient, -0.2; P = 0.038). The strongest predictor associated with LN count was the pathologist, with 2 groups of pathologists counting an average 7.7 (P < 0.001) and 6.42 (P = 0.001) fewer LNs per case compared to the referent group.
CONCLUSIONS: Our study confirms that LN count varies markedly. Although not the only contributor, the pathologist, we found, was the most significant determining factor in LN count variation. This highlights the need to exercise caution when drawing conclusions from published LN counts in endometrial cancer research.

Chu ES, Yow CM
Modulation of telomerase and signal transduction proteins by hexyl-ALA-photodynamic therapy (PDT) in human doxorubicin resistant cancer cell models.
Photodiagnosis Photodyn Ther. 2012; 9(3):243-55 [PubMed]

AIMS: This study employed a doxorubicin resistant (MES-SA-Dx5) human uterine sarcoma cell line and its counterpart (MES-SA), to elucidate the efficacy of aminolevulinic acid-hexylester (hexyl-ALA) mediated PDT at molecular and transcriptional levels.
METHODS: Hexyl-ALA generated protoporphyrin IX in both cells were determined by molecular probes using Confocal Laser Scanning Microscopy. The hexyl-ALA-PDT induced signal transduction proteins and mode of cell death were quantitated by CASE ELISA assays and DAPI staining. The modulation of hTERT mRNA expression and telomerase activity were investigated by TaqMan real-time PCR and ELISA respectively. Hexyl-ALA-PDT mediated cell migratory effect was determined by wound-healing assay.
RESULTS: The results demonstrated that mitochondria were the major target of hexyl-ALA. At LD(30), hexyl-ALA-PDT significantly provoked an up-regulation of phosphorylated p38MAPK and JNK proteins in both cells. Hexyl-ALA-PDT down-regulated hTERT (a catalytic subunit of telomerase) mRNA expression and showed a strong correlation with diminished telomerase activity in both cells (MES-SA: r(2) = 0.9932; MES-SA-Dx5: r(2) = 0.9775). The suppression of cell migratory effect in both cells was obtained after hexyl-ALA-PDT. Further, 50% and 30% of apoptotic cells were attained at LD(50), for wild-type and drug resistant cells respectively. Unlike the wild-type, a higher PDT dose was crucial to induce apoptosis in the drug resistant cells.
CONCLUSIONS: Our study provides the first evidence that p38MAPK and JNK kinases played a vital role in triggering hexyl-ALA-PDT-induced apoptosis, down-regulated hTERT mRNA expression and telomerase activity in both proposed cells. In vivo studies are worth examining for the benefit of clinical applications in drug resistant cancers and PDT development.

Stamatopoulos CP, Mikos T, Grimbizis GF, et al.
Value of magnetic resonance imaging in diagnosis of adenomyosis and myomas of the uterus.
J Minim Invasive Gynecol. 2012 Sep-Oct; 19(5):620-6 [PubMed]

STUDY OBJECTIVE: To estimate the diagnostic performance of magnetic resonance imaging (MRI) in detection of myomas and adenomyosis of the uterus.
DESIGN: Prospective cohort observational study (Canadian Task Force classification II-2).
SETTING: Department of obstetrics and gynecology, tertiary academic hospital.
PATIENTS: One hundred fifty-three consecutive women with an enlarged uterus accompanied by gynecologic symptoms and/or with an asymptomatic pelvic mass.
INTERVENTION: Total abdominal hysterectomy. All patients underwent MRI before the operation.
MEASUREMENTS AND MAIN RESULTS: The sensitivity, specificity, positive, and negative predictive value of MRI for the diagnosis of uterine pathology was calculated using histologic findings as the standard criterion for final diagnosis. Receiver operating characteristics curves were constructed to describe the diagnostic performance of MRI. In the diagnosis of myomas, MRI demonstrated sensitivity of 94.1%, specificity of 68.7%, PPV of 95.7%, and NPV of 61.1%. In the diagnosis of adenomyosis, MRI demonstrated sensitivity of 46.1%, specificity of 99.1%, PPV of 92.3%, and NPV of 88.5%. The area under the curve (AUC) for the diagnostic performance of MRI in the detection of myomas and adenomyosis was 0.81 and 0.73, respectively. Uterine sarcoma was diagnosed in 5 patients; in these cases, MRI demonstrated sensitivity of 60.0%, specificity of 99.2%, PPV of 75.0%, and NPV of 98.4%. The AUC for MRI in the diagnosis of uterine sarcomas was 0.80.
CONCLUSIONS: MRI exhibits a high AUC for the diagnosis of both adenomyosis and myomas. The PPV of MRI in the diagnosis of adenomyosis and myomas of the uterus is high as well. MRI seems to be a useful technique in everyday clinical practice in the diagnostic approach of these common conditions, enabling clinicians to select the most appropriate management.

Makino K, Kawamura K, Sato W, et al.
Inhibition of uterine sarcoma cell growth through suppression of endogenous tyrosine kinase B signaling.
PLoS One. 2012; 7(7):e41049 [PubMed] Article available free on PMC after 01/10/2013

Uterine leiomyosarcoma is an aggressive tumor typically found at advanced stages due to difficulties with early diagnosis. Because uterine leiomyosarcoma is resistant to conventional radiation and chemotherapy, the development of more potent medical therapeutics is anticipated. Using quantitative real-time RT-PCR and immunostaining, we found the expression of brain-derived neurotrophic factor (BDNF) and neurotropin-4/5, together with their receptor, tyrosine kinase B (TrkB), in different uterine sarcoma cell lines and primary tumor samples from uterine leiomyosarcoma patients. We noted that levels of BDNF were more abundant than those of neurotropin-4/5. Moreover, the expression of TrkB and its ligands was elevated in a multidrug-resistant cell line and samples obtained from patients with leiomyosarcoma. In cultured uterine sarcoma cells, inhibition of endogenous TrkB signaling by treatment with either the soluble TrkB ectodomain or the Trk receptor inhibitor, K252a, suppressed cell proliferation and increased apoptosis based on cell viability and proliferation, in situ terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end-labeling and caspase-3/7 assays, whereas an inactive plasma membrane nonpermeable K252b was ineffective. Correspondingly, treatment with exogenous BDNF increased cell proliferation. In in vivo studies in athymic nude mice bearing multidrug-resistant uterine sarcoma cell tumors, we demonstrate suppression of tumor growth by treatment with K252a, but not K252b, as reflected by decreased cell proliferation and increased levels of apoptosis and caspase-3/7 activities without obvious side effects. Our findings indicated that endogenous signaling of the TrkB pathway contributed to uterine sarcoma cell growth, and inhibition of TrkB signaling in these tumors could provide a novel medical therapy for patients with uterine sarcomas.

Eto T, Saito T, Kasamatsu T, et al.
Clinicopathological prognostic factors and the role of cytoreduction in surgical stage IVb endometrial cancer: a retrospective multi-institutional analysis of 248 patients in Japan.
Gynecol Oncol. 2012; 127(2):338-44 [PubMed]

OBJECTIVE: To evaluate clinicopathological prognostic factors and the impact of cytoreduction in patients with surgical stage IVb endometrial cancer (EMCA).
METHODS: The records of 248 patients with stage IVb EMCA who underwent primary surgery including hysterectomy at multiple institutions from 1996 to 2005 were retrospectively analyzed. Data regarding disease distribution, surgical procedures, adjuvant therapy, and survival times were collected. Univariate and multivariate analyses were performed to identify factors associated with overall survival (OS).
RESULTS: The median OS was 24 months. The most common histological types were endometrioid (grade 1: 15%, grade 2: 20%, grade 3: 24%) and serous (17%). The most common sites of intra-abdominal metastases were pelvis (65%), ovaries (58%), omentum (58%), retroperitoneal lymph nodes (52%), and upper abdominal peritoneum (44%). In 93 patients with extra-abdominal metastases, the most common site was the lung (n=49). Complete resection of extra-abdominal metastases was achieved in only 13 patients. Complete resection of intra-abdominal metastases was achieved in 101 patients, 52 had ≤1 cm residual disease, and 95 had >1cm residual disease; the median OS times in these groups were 48, 23, and 14 months, respectively (p<0.0001). Multivariate analysis showed that performance status, histology/grade, adjuvant treatment, and intra-abdominal residual disease were independent prognostic factors. Intra-abdominal residual disease was an independent prognostic factor in patients with and without extra-abdominal metastases.
CONCLUSIONS: Cytoreductive surgery and adjuvant therapy may improve survival in stage IVb EMCA, particularly in patients with favorable prognostic factors, even in the presence of extra-abdominal metastases.

Durnali A, Tokluoğlu S, Özdemir N, et al.
Prognostic factors and treatment outcomes in 93 patients with uterine sarcoma from 4 centers in Turkey.
Asian Pac J Cancer Prev. 2012; 13(5):1935-41 [PubMed]

INTRODUCTION: Uterine sarcomas are a group of heterogenous and rare malignancies of the female genital tract and there is a lack of consensus on prognostic factors and optimal treatment. OBJECTIVE AND METHODOLOGY: To perform a retrospective evaluation of clinicopathological characteristics, prognostic factors and treatment outcomes of 93 patients with uterine sarcomas who were diagnosed and treated at 4 different centers from November 2000 to October 2010.
RESULTS: Of the 93 patients, 58.0% had leiomyosarcomas, 26.9% malignant mixed Mullerian tumors, 9.7% endometrial stromal sarcomas, and 5.4% other histological types. According to the last International Federation of Gynecology and Obstetrics (FIGO) staging, 43.0% were stage I, 20.4% were stage II, 22.6% were stage III and 14.0 % were stage IV. Median relapse free survival (RFS) was 20 months (95% confidence interval (CI), 12.4-27.6 months), RFS after 1, 2, 5 years were 66.6%, 44.1%, 16.5% respectively. Median overall survival (OS) was 56 months (95% CI, 22.5-89.5 months), and OS after 1, 2, 5 years was 84.7%, 78%, 49.4% respectively. Multivariate analysis showed that age≥60 years and high grade tumor were significantly associated with poor OS and RFS; patients administered adjuvant treatment with sequential chemotherapy and radiotherapy had longer RFS time. Among patients with leiomyosarcoma, in addition to age and grade, adjuvant treatment with sequential chemotherapy and radiotherapy after surgery had significant effects on OS.
CONCLUSION: Uterine sarcomas have poor progrosis even at early stages. Prognostic factors affecting OS were found to be age and grade.