Uterine sarcoma is a rare kind of cancer in which the cells in the muscles or other supporting tissues of the uterus become cancerous, and represents 1% of gynaecological cancers overall. This is very different to endometrial (uterus) cancer - see above. There are two main histological sub-types; leiomyosarcoma, and stromal sarcoma. A known risk factor for developing uterine sarcoma is prior radiotherapy to the pelvic area, this is estimated to account for between 10% to 25% of cases.
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MeSH term: Uterine Neoplasms
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Circulating Protein Biomarkers to Differentiate Uterine Sarcomas from Leiomyomas.
Anticancer Res. 2019; 39(8):3981-3989 [PubMed] Related Publications
Preliminary utilization of radiomics in differentiating uterine sarcoma from atypical leiomyoma: Comparison on diagnostic efficacy of MRI features and radiomic features.
Eur J Radiol. 2019; 115:39-45 [PubMed] Related Publications
METHODS: 78 patients (29 sarcomas, 49 leiomyomas) imaged with pelvic MRI prior to surgery were included in this retrospective study. Certain clinical and MRI features were evaluated for one lesion per patient. Radiological diagnosis was made based on MRI features. A radiomic model using automated texture analysis based on ADC maps was built to predict pathological results. The association between MRI features and pathological results was determined by multivariable logistic regression after controlling for other variables in univariate analyses with P < 0.05. The diagnostic efficacy of radiologists and radiomic model were compared by area under the receiver-operating characteristic curve (AUC), sensitivity, specificity and accuracy.
RESULTS: In univariate analyses, patient's age, menopausal state, intratumor hemorrhage, tumor margin and uterine endometrial cavity were associated with pathological results, P < 0.05. Patient's age, tumor margin and uterine endometrial cavity remained significant in a multivariable model, P < 0.05. Diagnosis efficacy of radiologists based on MRI reached an AUC of 0.752, sensitivity of 58.6%, specificity of 91.8%, and accuracy of 79.5%. The optimal radiomic model reached an AUC of 0.830, sensitivity of 76.0%, average specificity of 73.2%, and accuracy of 73.9%.
CONCLUSIONS: Ill-defined tumor margin and interrupted uterine endometrial cavity of older women were predictors of uterine sarcoma. Radiomic analysis was feasible. Optimal radiomic model showed comparable diagnostic efficacy with experienced radiologists.
Identification of endometrial cancers and atypical hyperplasia: Development and validation of a simplified system for ultrasound scoring of endometrial pattern.
Maturitas. 2019; 123:15-24 [PubMed] Related Publications
STUDY DESIGN: Endometrial pattern was correlated with endometrial pathology in consecutive women with PMB in both a derivation study (N = 164) and a validation study (N = 711). Logistic regression was used to derive and validate two scoring systems (A and B) for prediction of EC/AH: scoring system A was Doppler score + interrupted endo-myometrial junction (IEJ) (2 points); and scoring system B was Doppler score + IEJ (1 point) + Irregular Endometrial Outline (IESO) by GIS (1 point); the Doppler score was based on the presence of more than one single or double vessel (1 point) + multiple vessels (1 point) + large vessels (1 point).
OUTCOME MEASURES: Diagnostic performance and calibration curves for identification of EC/AH.
RESULTS: Both scoring systems had good observer agreement.
VALIDATION DATA: Scoring was most effective with endometrial thickness (ET) ≥ 8 mm. Both scoring systems were well calibrated and performed satisfactorily in women with ET ≥ 8 mm. The sensitivity and specificity of a score of ≥ 2 points in system A were 92% and 84%; the respective values were 89% and 88% in system B.
CONCLUSIONS: Scoring was highly efficient in identifying EC/AH. Four risk groups of EC/AH may guide the management of women with PMB: very low (ET < 4 mm), low (ET 4-7.9 mm), intermediate (ET ≥ 8 mm and score < 2 points) and high risk (ET ≥ 8 mm and score ≥ 2 points).
Metastatic low-grade endometrial stromal sarcoma of uterus presenting as a primary pancreatic tumor: case presentation and literature review.
Diagn Pathol. 2019; 14(1):30 [PubMed] Free Access to Full Article Related Publications
CASE PRESENTATION: A 50-year old female patient was investigated for a cause of abdominal discomfort. She had a 2-year history of menorrhagia and dysmenorrhea which was ascribed to a fibroid uterus. On imaging, she was found to have a large solid and cystic mass in the tail of the pancreas. Imaging also confirmed a fibroid uterus. A distal pancreatectomy and splenectomy showed a 9 cm circumscribed mass within, and grossly confined to, the parenchyma of the pancreatic tail. Microscopically, the pancreatic lesion was lobulated, and well-circumscribed, but focally infiltrative. It comprised sheets of uniform spindled to epithelioid cells with round to oval nuclei, coarse to vesicular chromatin, visible nucleoli, nuclear grooves and clear to eosinophilic cytoplasm. Prominent arterioles were identified. The stroma was collagenized in areas. Occasional hemosiderin-laden macrophages were seen, and focal cystic change was present. There was no evidence of nuclear pleomorphism, mitotic activity or necrosis, and there was no evidence of endometriosis despite multiple sections being taken. Immunohistochemistry showed that the tumor cells were positive for CD10, estrogen receptor (ER), progesterone receptor (PR), Wilms tumor-1 (WT-1) and smooth muscle actin (SMA). RNA sequencing detected a PHF1 rearrangement. The morphological, immunohistochemical and molecular features were of a low-grade endometrial stromal sarcoma (LG-ESS). Subsequent total hysterectomy and bilateral salpingo-oophorectomy 3 months later, showed uterine fibroids and a 5 cm low-grade endometrial stromal sarcoma confined to the uterus, with lymphatic invasion.
CONCLUSIONS: To the best of our knowledge, this is the first documented case of metastatic endometrial stromal sarcoma of uterus presenting as a primary pancreatic neoplasm. An unexpected extra-uterine location and unusual presentation of ESS may make the diagnosis challenging, despite classic histological features. Morphological, immunohistochemical and molecular findings must be combined to render the correct diagnosis.
Predictive Histologic Factors in Carcinosarcomas of the Uterus: A Multi-institutional Study.
Int J Gynecol Pathol. 2019; 38(3):205-215 [PubMed] Related Publications
Carcinosarcoma of the uterine cervix: a rare pathological finding originating from mesonephric remnants.
BMJ Case Rep. 2019; 12(3) [PubMed] Related Publications
The prognostic significance of aortic lymph node metastasis in endometrial cancer: Potential implications for selective aortic lymph node assessment.
Gynecol Oncol. 2019; 153(3):505-510 [PubMed] Article available free on PMC after 01/06/2020 Related Publications
METHODS: Using data from the SEER 18 Registries we identified 3650 women with LN positive (stage IIIC) EC. We used Kaplan-Meier curves and log-rank tests to compare mortality between women with stage IIIC1 and IIIC2 disease. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between stage III sub-stage (IIIC1 vs. IIIC2) and survival.
RESULTS: Endometrioid tumors were more common among women with stage IIIC1 than IIIC2 tumors (62.5% vs. 54.3%) while, non-endometrioid histologies were more common among stage IIIC2. In the multivariable model, stage IIIC2 was associated with higher all-cause (HR = 1.44, 95% CI = 1.22-1.69) and EC-specific mortality (HR = 1.49, 95% CI = 1.25-1.77) compared with IIIC1. Women with non-endometrioid EC had poor survival, in particular, women with carcinosarcomas had higher EC-specific mortality compared to women with endometrioid EC (HR = 3.32, 95% CI = 2.71-4.07). When stratifying women according to substage, older age and non-endometrioid histology were associated with higher EC-specific mortality. Compared to women with a pelvic-only LN dissection, women with pelvic and aortic dissections had lower all-cause (HR = 0.74, 95% CI = 0.63-0.88) and EC-specific (HR = 0.79, 95% CI = 0.66-0.95) mortality.
CONCLUSION: Women with aortic LN positive EC are more likely to die from their disease. Older women and non-endometrioid histologies are more likely to have aortic LN involvement. Compared to women with a pelvic-only LN dissection, women with pelvic and aortic dissections had lower EC mortality.
Investigating the diagnostic value of quantitative parameters based on T2-weighted and contrast-enhanced MRI with psoas muscle and outer myometrium as internal references for differentiating uterine sarcomas from leiomyomas at 3T MRI.
Cancer Imaging. 2019; 19(1):20 [PubMed] Article available free on PMC after 01/06/2020 Related Publications
MATERIALS AND METHODS: The institutional review board approved the study. Sixty-five women confirmed to have a total of 105 lesions participated. Routine pelvic MRI sequences, T2 map and CE-MRI images were performed preoperatively using a 3 T MR scanner. Six quantitative metrics-T2 mapping parameter, T2 scaled ratio, tumor myometrium contrast ratio on T2, tumor psoas contrast ratio on T2, tumor myometrium contrast-enhanced ratio, and tumor psoas contrast-enhanced ratio-were extracted from the acquired image sets. Chi-square test was used to compare the percentage of malignant lesions with the central necrosis to the corresponding percentage for the benign masses. Using the area under receiver operating characteristic (AUC) curve, the performance of different metrics for distinguishing uterine sarcomas from leiomyomas was measured. Moreover, for each metric, we extracted the optimal cut-off value. The values of sensitivity, specificity, negative predictive value, and positive predictive value were calculted for the classifiers based on different metrics.
RESULTS: The average age, average lesion size, and proportion of premenopausal women in benign and malignant groups were comparable in our dataset. The signal intensity of uterine sarcomas at T2-weighted sequences was significantly higher than that of leiomyomas (p < 0.001), while intensity at T1-weighted sequences exhibited no significant difference between the two masses (p = 0.201). Our data also suggested that a central necrosis was ten times more common among malignant lesions compared to benign ones (p < 0.001). Among different metrics, T2 mapping parameter achieved the highest AUC value and accuracy in differentiating two groups. Three measures-T2 scaled ratio, tumor myometrium contrast ratio on T2, and tumor myometrium contrast-enhanced ratio-achieved a sensitivity of 100%, therefore none of the malignant lesions would have been missed if these metrics had been adopted in patient management.
CONCLUSIONS: The findings suggested that the evaluated metrics could be useful in the preoperative assessment of myometrial masses to differentiate uterine sarcomas from leiomyomas. The proposed framework has major implications for improving current practice in the management of myometrial masses.
Treatment of uterine high-grade endometrial stromal sarcoma with apatinib combined with chemotherapy: A case report.
Medicine (Baltimore). 2019; 98(13):e15050 [PubMed] Article available free on PMC after 01/06/2020 Related Publications
PATIENTS CONCERNS: A 54-years-old Chinese woman complained of intermittent pain in the waist and abdomen for 4 months. The patient was diagnosed as uterine fibroids before operation. The surgeon performed a total hysterectomy with bilateral salpingo-oophorectomy, resection of peritoneal disseminated lesions, and the pathological examination revealed a HGESS.
DIAGNOSIS: Uterine HGESS stage IV with lung metastases.
INTERVENTIONS: The patient underwent surgery, chemotherapy, chemotherapy combined with apatinib, apatinib maintenance therapy, and radioactive particle implantation for lung metastasis.
OUTCOMES: The patient experienced the above interventions and achieved good results. And continue oral apatinib (500 mg daily) as maintenance therapy. It has been 16 months since the initial diagnosis, and the patient is still in follow-up.
LESSONS: Apatinib combined with chemotherapy and apatinib monotherapy as maintenance therapy could be a new therapeutic strategy for ESS.
The Usefulness of Immunohistochemistry in the Differential Diagnosis of Lesions Originating from the Myometrium.
Int J Mol Sci. 2019; 20(5) [PubMed] Article available free on PMC after 01/06/2020 Related Publications
Role of epithelial-mesenchymal transition factors in the histogenesis of uterine carcinomas.
Virchows Arch. 2019; 475(1):85-94 [PubMed] Related Publications
Current state of the art and emerging pharmacotherapy for uterine leiomyosarcomas.
Expert Opin Pharmacother. 2019; 20(6):713-723 [PubMed] Related Publications
AREAS COVERED: The aim of this review is to describe the current pharmacotherapy for ULMS, including the ongoing clinical trials.
EXPERT OPINION: Surgery is the standard treatment for patients with early-stage ULMS. In this setting, the role of adjuvant therapies is still unclear. In the case of advanced, persistent, or recurrent ULMS, chemotherapy is the standard care with the most frequently used drug being doxorubicin. As the outcomes for patients with the currently available conventional single or combined regimens are far from being satisfactory, new alternative and innovative medical compounds have or are being evaluated. Recently, pazopanib, and olaratumab, two innovative targeted drugs, have been approved by the Food and Drug Administration (FDA) for treating advanced soft-tissue sarcoma, including ULMS. However, further clinical investigations into new and innovation therapeutic options are warranted.
The Role of KRAS in Endometrial Cancer: A Mini-Review.
Anticancer Res. 2019; 39(2):533-539 [PubMed] Related Publications
Beyond Smooth Muscle-Other Mesenchymal Neoplasms of the Uterus.
Surg Pathol Clin. 2019; 12(1):107-137 [PubMed] Related Publications
Mullerian adenosarcoma (heterologous) of uterine cervix with sarcomatous overgrowth: A case report with review of the literature.
Indian J Pathol Microbiol. 2019 Jan-Mar; 62(1):139-141 [PubMed] Related Publications
Cytological features of uterine carcinosarcoma: A retrospective study of 20 cases with an emphasis on the usefulness of endometrial cytology.
Diagn Cytopathol. 2019; 47(6):547-552 [PubMed] Related Publications
METHODS: Patients histopathologically diagnosed with endometrial carcinosarcoma who underwent preoperative endometrial or endocervical cytological examination were enrolled. The endometrial and/or endocervical specimens were conventionally stained with Papanicolaou stain, and the cytological characteristics, including arrangement and shape of the neoplastic cells, and the nuclear and cytoplasmic features were reviewed.
RESULTS: Twenty patients were enrolled in the study. In the endometrial specimens, carcinomatous component was detected in almost all cases (94.4%), including those suspicious of carcinoma despite a small volume of carcinomatous cells. Sarcomatous component was observed in 6 of 18 cases (33.3%) and was significantly more frequently detected in the heterologous type (5 of 9 cases) compared to the homologous type (1 of 9 cases) (P = 0.046). In the endocervical specimens, carcinomatous component was present in 76.5% of cases, but sarcomatous component was detected in only 17.6% of cases.
CONCLUSION: Although endocervical cytology can detect the carcinomatous component in more than 50% of endometrial carcinosarcoma cases, it has lesser capability to detect sarcomatous component. In conclusion, endometrial cytological examination is a more useful and accurate method to detect sarcomatous component of endometrial carcinosarcoma, particularly in the heterologous type, compared to endocervical cytological examination.
The Effect of Fucoidan, a Potential New, Natural, Anti-Neoplastic Agent on Uterine Sarcomas and Carcinosarcoma Cell Lines: ENITEC Collaborative Study.
Arch Immunol Ther Exp (Warsz). 2019; 67(2):125-131 [PubMed] Article available free on PMC after 01/06/2020 Related Publications
Analysis of uterine corporeal mesenchymal tumors occurring after menopause.
BMC Womens Health. 2019; 19(1):13 [PubMed] Article available free on PMC after 01/06/2020 Related Publications
METHODS: We retrospectively reviewed the cases of women who underwent surgery for uterine mesenchymal tumors at our hospital.
RESULTS: Among 487 operated cases, 447 tumors occurred in the premenopausal period and 40 occurred in the postmenopausal period. Uterine sarcomas were observed in 5 cases (1.1%) during the premenopausal period and in 11 cases (28%) during the postmenopausal period. Among the postmenopausal patients, age, age at menopause, body mass index (BMI), tumor size, incidence of abnormal vaginal bleeding, serum tumor marker levels (cancer antigen 125, carbohydrate antigen 19-9, and carcinoembryonic antigen), and serum lactate dehydrogenase values were not significantly different between patients with benign tumors and those with malignant tumors. On the other hand, the incidence to have abnormal signal on MRI was significantly higher in patients with malignant tumors than in patients with benign tumors.
CONCLUSION: In our hospital, the incidence of malignant tumors in women with uterine corporeal mesenchymal tumors was much higher in postmenopausal patients than in premenopausal patients. Because it is generally not easy to diagnose uterine sarcomas before surgery, surgery should be positively considered when uterine sarcomas cannot be ruled out for patients in the postmenopausal period.
Feasibility of myomatous tissue extraction in laparoscopic surgery by contained in - bag morcellation: A retrospective single arm study.
Int J Surg. 2019; 62:22-27 [PubMed] Related Publications
MATERIAL AND METHODS: We conducted a retrospective single center case - control study on 239 patients, between 01.05.2014 and 31.12.2017 for uterine myomata, presumed to be benign. The analyzed parameters were the method for contained specimen retrieval, the time of bag manipulation, practicability of action and the perioperative complications rate. The present work has been reported in accordance with the STROCSS criteria and guidelines .
RESULTS: the main laparoscopic interventions were myomectomy (n = 148 cases) and LASH (laparoscopic supracervical hysterectomy) (n = 68 cases), LASH with bilateral salpingectomy (n = 7), LASH and bilateral adnexectomy (n = 3), LTH (laparoscopic total hysterectomy) (n = 3), LTH and bilateral adnexectomy (n = 1), radical LTH with lymphonodectomy (n = 2), LTH with bilateral salpingectomy (n = 1) and adenomyomectomy (n = 6). In 3 cases using contained closed bags, there was an evidence of malignancy in the pathological sections: leiomyosarcoma (n = 1) and endometrial carcinoma (n = 2). There were no adverse events and no intra - or postoperative bag - induced complications. Regarding the intraoperative duration, the time of bag introduction was about 7 min, and morcellation approximately 12 min.
CONCLUSION: in - bag morcellation through endobag (Morsafe
Unexpected malignant uterine pathology: Incidence, characteristics and outcome in a large single-center series of hysterectomies for presumed benign uterine disease.
Gynecol Oncol. 2019; 153(1):49-54 [PubMed] Related Publications
METHODS: Patients who underwent hysterectomy for presumed benign conditions between 2003 and 2016 were identified. In cases of unexpected malignancies of the uterine corpus (UUM), available tissue samples were collected and a specialized gynecopathological review was performed.
RESULTS: A total of 10,756 patients underwent hysterectomy for benign indications. After chart and gynecopathological review, 45/10,756 (0.42%) cases of unexpected uterine malignancies were confirmed. 33/45 (73.3%) were endometrial carcinomas (UEC) and 12/45 (26.7%) were uterine sarcomas (UUS). 27/33 (81.8%) UEC were FIGO IA, 5/33 (15.2%) FIGO IB and 1/33 (3%) FIGO stage II disease. Endometrioid and serous histotype were present in 31/33 (93.9%) and in 2/33 (6.1%) cases, respectively. 8/12 (66.7%) USS were early stage (FIGO IA or IB); only 3/12 (25.0%) were diagnosed at an advanced stage (≥FIGO II). Fatal outcome was observed in 1 patient diagnosed with UEC and 3 patients diagnosed with UUS.
CONCLUSION: Our study shows that diagnosis of UUM is rare (0.42%). The majority of UUM tend to be early stage, making preoperative diagnosis difficult. In case of UEC, patient outcome is generally favorable. Nevertheless, the appropriate surgical approach for hysterectomy for a benign indication should be chosen carefully, taking all preoperative findings into account. Patients should always be informed about the residual risk of UUM.
A machine learning approach for distinguishing uterine sarcoma from leiomyomas based on perfusion weighted MRI parameters.
Eur J Radiol. 2019; 110:203-211 [PubMed] Related Publications
MATERIALS AND METHODS: Forty-two women confirmed to have a total of 60 masses (10 uterine sarcomas and 50 benign leiomyomas) were included. The reference diagnosis was based on postoperative histopathological examination. All women underwent the standard MRI protocol with 3-Tesla MR imager (Magnetom Trio, Siemens, Erlangen, Germany) for assessment of myometrial masses, followed by PWI. For each mass, two regions of interest (ROI) were outlined manually by an experienced radiologist; one (ROI
RESULTS: None of the parameters extracted from ROI
CONCLUSION: Although none of the PWI parameters differed significantly between benign and malignant lesions, when the information provided by the extracted features was aggregated using a machine learning method, a promising discriminative power was obtained. This suggests that the proposed model for combining the PWI parameters is potentially useful for differentiating uterine sarcoma from leiomyomas.
Issues in the Differential Diagnosis of Uterine Low-grade Endometrioid Carcinoma, Including Mixed Endometrial Carcinomas: Recommendations from the International Society of Gynecological Pathologists.
Int J Gynecol Pathol. 2019; 38 Suppl 1:S25-S39 [PubMed] Article available free on PMC after 01/06/2020 Related Publications
Management of uterine sarcomas and prognostic indicators: real world data from a single-institution.
BMC Cancer. 2018; 18(1):1247 [PubMed] Article available free on PMC after 01/06/2020 Related Publications
METHODS: We retrospectively analyzed all female patients with uterine sarcomas treated in our institution over the last 17 years. Clinico-pathological data, treatments and outcomes were recorded. Kaplan-Meier curves were plotted and time-to-event analyses were estimated using Cox regression.
RESULTS: Data were retrieved from 61 women with a median age of 53 (range: 27-78) years, at diagnosis. Fifty-one patients were diagnosed with leiomyosarcoma (LMS), 3 with high grade endometrial stromal sarcoma (ESS), 5 with undifferentiated uterine sarcoma (UUS), 1 with Ewing sarcoma (ES) and 1 with Rhabdomyosarcoma (RS). 24 cases had stage I, 7 stage II, 14 stage III and 16 stage IV disease. Median disease-free survival (DFS) in adjuvant approach was 18.83 months, and median overall survival (OS) 31.07 months. High mitotic count (> 15 mitoses) was significantly associated with worse OS (P < 0.001) and worse DFS (P = 0.028).
CONCLUSIONS: Mitotic count appears to be independent prognostic factor while further insights are needed to improve adjuvant and palliative treatment of uterine sarcomas.
Endometrial stromal sarcoma in a 27-year-old woman. Case report and literature review.
Rom J Morphol Embryol. 2018; 59(3):933-938 [PubMed] Related Publications
Aromatase inhibitor therapy for endometrial stromal sarcoma - two-centre experience.
Ginekol Pol. 2018; 89(11):607-610 [PubMed] Related Publications
MATERIAL AND METHODS: We retrospectively identified cases treated for ESS with aromatase inhibitors at our institutions. There were five patients with advanced or unresectable recurrent estrogen, progesterone and androgen receptor-positive ESS, treated with aromatase inhibitors: letrozole or anastrozole (at a daily dose of 2.5 mg and 1 mg, respectively), as first-line endocrine therapy in all but one case treated following progression with megestrol acetate.
RESULTS: Disease stabilization was achieved in four cases (80%), including two with long-term progression-free survival for up to 10 years attained under letrozole treatment, and one case after prior progestin treatment. During therapy, no substantial toxicity was observed.
CONCLUSIONS: Aromatase inhibitors as first- or second-line endocrine treatment achieve disease control in most steroid receptor positive ESS. Our series of cases is evidence of aromatase inhibitors efficacy as long-term endocrine treatment option for ESS patients.
Ultrasonographic Findings of Uterine Carcinosarcoma.
Gynecol Obstet Invest. 2019; 84(3):277-282 [PubMed] Related Publications
METHODS: Seventy-five patients (mean age, 58.6 years) with pathologically proven UCS who were treated at our hospital from January 2003 to December 2015 were retrospectively recruited. The clinical features and preoperative findings on transvaginal sonography (TVS) were investigated.
RESULTS: Eighty percent of the patients were postmenopausal. The primary symptoms were postmenopausal abnormal uterine bleeding (57.3%), irregular menstruation (18.7%), vaginal discharge (10.7%) and the presence of a uterine mass or others (13.3%). The tumor marker CA125 was evaluated in 43 women and was found to be elevated in 15 (34.9%); in 60% of those women (9/15), the CA125 level was lower than 200U/ml. According to the frequency of the different types of lesions observed by ultrasonic imaging, we decided to categorize the lesions into 3 different groups as follows: Group I, intrauterine tumors (73.33%); group II, intra-myometrial tumors (13.33%); and group III, intra-endometrial tumors (13.33 %).
CONCLUSION: Combined with the clinical features, the characteristics demonstrated by TVS provide evidence for an indication of the presence of UCS and could contribute to clinical decision-making.
Low-grade endometrial stromal sarcoma combined with leiomyoma (stromomyoma): A bizarre tumor of the uterus in a premenopausal woman.
J Exp Ther Oncol. 2018; 12(4):281-286 [PubMed] Related Publications
Impact of copper and iron binding properties on the anticancer activity of 8-hydroxyquinoline derived Mannich bases.
Dalton Trans. 2018; 47(47):17032-17045 [PubMed] Related Publications
Analysis of mutational signatures in primary and metastatic endometrial cancer reveals distinct patterns of DNA repair defects and shifts during tumor progression.
Gynecol Oncol. 2019; 152(1):11-19 [PubMed] Related Publications
METHODS: Whole-exome sequencing MC3 data from primary endometrioid and serous carcinomas (n = 232) and uterine carcinosarcomas (n = 57) from The Cancer Genome Atlas (TCGA), and matched primary and metastatic ECs (n = 61, 26 patients) were reanalyzed, subjected to mutational signature analysis using deconstructSigs, and correlated with clinicopathologic and genomic data.
RESULTS: POLE (ultramutated) and MSI (hypermutated) molecular subtypes displayed dominant mutational signatures associated with POLE mutations (15/17 cases) and microsatellite instability (55/65 cases), respectively. Most endometrioid and serous carcinomas of copy-number low (endometrioid) and copy-number high (serous-like) molecular subtypes, and carcinosarcomas displayed a dominant aging-associated signature 1. Only 15% (9/60) of copy-number high (serous-like) ECs had a dominant signature 3 (homologous recombination DNA repair deficiency (HRD)-related), a prevalence significantly lower than that found in high-grade serous ovarian carcinomas (54%, p < 0.001) or basal-like breast cancers (46%, p < 0.001). Shifts from aging- or POLE- to MSI-related mutational processes were observed in the progression from primary to metastatic ECs in a subset of cases.
CONCLUSIONS: The mutational processes underpinning ECs vary even among tumors of the same TCGA molecular subtype and in the progression from primary to metastatic ECs. Only a minority of copy-number high (serous-like) ECs display genomics features of HRD and would likely benefit from HRD-directed therapies.
Prognostic factors impacting survival in early stage uterine carcinosarcoma.
Gynecol Oncol. 2019; 152(1):31-37 [PubMed] Article available free on PMC after 01/01/2020 Related Publications
METHODS: We performed a retrospective cohort study of women with stage I or II uterine carcinosarcoma at our institution between March 1990 and June 2016. All pathology had been reviewed and confirmed by gynecologic pathologists. Data were extracted from the electronic medical record. Descriptive and comparative statistics were used to compare clinicopathologic characteristics. Univariable and multivariable analyses were performed for survival outcomes.
RESULTS: 140 patients were identified. Median age was 67 years (range: 36-91). Median follow-up was 39.1 months (2.9-297.4). The majority of patients had stage IA (67%) versus stage IB (21%) or stage II (11%) disease. The majority of patients (63%) received adjuvant treatment: vaginal brachytherapy only (14%); whole pelvic radiation therapy only (16%); chemotherapy only (n = 13, 9%); combination chemotherapy and vaginal brachytherapy (15%); combination chemotherapy and whole pelvic radiation (9%). 52 patients (37%) received no adjuvant therapy. Median overall survival (OS) was 48.0 months (95% CI 32.7-80.9). On multivariable analysis for OS, advancing age (HR 1.05, 95% CI 1.03-1.08, p < 0.001), higher stage (stage IB: HR 1.64, 95% CI 0.91-2.95, p = 0.10; stage II: HR 3.04, 95% CI 1.51-6.13, p = 0.002), and the presence of a rhabdomyosarcoma component (HR 1.66, 95% CI 1.02-2.70, p = 0.04) were significantly associated with worse OS.
CONCLUSIONS: Advancing age, stage, and the presence of a rhabdomyosarcoma component were all associated with worse OS in patients with early stage uterine carcinosarcoma. New treatment algorithms should incorporate factors aside from stage alone.