Endometrial (Uterus) Cancer
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Endometrial cancer is a malignancy of the endometrium (the inner lining of the uterus, or womb) and is the most common gynaecological cancer, and accounts for 13% of all cancers in women. It is most frequently in women over age 50. A know risk factor is prior oestrogen-replacement therapy (however, oestrogen replacement also lowers risk of heart disease). Symptoms can include pelvic pain, and blood-soaked discharge - though these are also common symptoms related to menopausal changes.

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Information for Patients and the Public
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Latest Research Publications

Information Patients and the Public (10 links)

Information for Health Professionals / Researchers (10 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Abid N, Mnif H, Mellouli M, et al.
Uterine tumour resembling ovarian sex cord tumours presenting as multiple endometrial and cervical uterine polyps: a case report.
Pathologica. 2014; 106(2):73-6 [PubMed] Related Publications
BACKGROUND: Uterine tumours resembling ovarian sex-cord tumours (UTROSCT) are very rare, benign uterine tumours, composed solely of sex cord elements. These tumours have a polyphenotypic immunophentype that favours a derivation from uterine mesenchymal stem cells.
CASE REPORT: A 43-year-old female presented with recurrent vaginal bleeding. On hysteroscopy, she had multiple endometrial and cervical polyps that were removed endoscopically. Histologically, the specimen contained epithelioid cells arranged in tubules, trabeculae and anastomosing cords, without significant cellular atypia or mitotic activity. Immunohistochemical studies were performed. The tumour was found to be diffusely positive for vimentin, calretinin and desmin, focally positive for cytokeratin, CD99 and inhibin and negative for chromogranin and CD10. A subsequent total hysterectomy was performed and revealed neoplastic infiltration of the myometrium.
CONCLUSION: A polyphenotypic immunophenotype is a characteristic feature of UTROSCT, and may be helpful in diagnosis and in exclusion of other lesions. Familiarity with this tumour by gynaecologists and pathologists is essential to avoid misdiagnosis:correct diagnosis of this neoplasm is important in patient management.

Related: Ovarian Cancer Cervical Cancer

Sciallis AP, Bedroske PP, Schoolmeester JK, et al.
High-grade endometrial stromal sarcomas: a clinicopathologic study of a group of tumors with heterogenous morphologic and genetic features.
Am J Surg Pathol. 2014; 38(9):1161-72 [PubMed] Related Publications
The existence of a "high-grade endometrial stromal sarcoma" category of tumors has been a controversial subject owing to, among other things, the difficulty in establishing consistent diagnostic criteria. Currently, the recommended classification for such tumors is undifferentiated uterine/endometrial sarcoma. Interest in this subject has recently increased markedly with the identification of recurrent molecular genetic abnormalities. At Mayo Clinic, a group of neoplasms has been observed that morphologically resemble, either cytologically or architecturally, classic "low-grade" endometrial stromal sarcoma but feature obvious deviations, specifically, 17 tumors with unequivocally high-grade morphology. These high-grade tumors displayed 3 morphologic themes: (1) tumors with a component that is identical to low-grade ESS that transitions abruptly into an obviously higher-grade component; (2) tumors composed exclusively of high-grade cells with uniform nuclear features but with a permeative pattern of infiltration; (3) tumors similar to the second group but with a different, yet characteristic, cytomorphology featuring enlarged round to ovoid cells (larger than those found in low-grade ESS) with smooth nuclear membranes and distinct chromatin clearing but lacking prominent nucleoli. We collected clinicopathologic data, applied immunohistochemical studies, and also tested tumors by fluorescence in situ hybridization for abnormalities in JAZF1, PHF1, YWHAE, and CCND1. Tumors from these 3 groups were found to be immunohistochemically and genetically distinct from one another. Most notable was the fact that category 3 contained all the cases that tested positive for YWHAE rearrangement, did not show any classic translocations for JAZF1, PHF1, or CCND1, often presented at a high stage, and behaved aggressively. This study demonstrates the morphologic, immunophenotypic, and molecular genetic heterogeneity that exists within "undifferentiated endometrial sarcomas" as currently defined and lends credence to the effort of subclassifying some tumors as truly "high-grade endometrial stromal sarcomas." Our study also shows that, in the context of undifferentiated endometrial sarcomas, recognition of cytomorphologic features on routine hematoxylin and eosin-stained sections may be used to select tumors with specific molecular genetic changes-that is, translocations involving YWHAE. Our conclusions will help further efforts towards proper sub-classification of these tumors which will aid in diagnosis and potentially affect clinical management.

Related: FISH

Pichatechaiyoot A, Buhachat R, Boonyapipat S, Kanjanapradit K
Radiation, chemotherapy or combined modality therapy in adjuvant treatment for stage III endometrial carcinoma in lower southern Thailand: disease recurrence and overall survival.
J Med Assoc Thai. 2014; 97(3):274-82 [PubMed] Related Publications
OBJECTIVE: To survey disease-free survival (DFS) and overall survival (OS) of patients with stage III endometrial carcinoma treated with post-operative radiation and/or chemotherapy
MATERIAL AND METHOD: The medical records of patients with surgical stage III endometrial carcinoma, and receiving adjuvant treatment between January 2003 and December 2012 were reviewed DFS and OS were analyzed using the Kaplan-Meier method and Cox proportional hazards model.
RESULTS: Of the 54 eligible patients, 61% underwent radiation, 19% chemotherapy, and 20% chemotherapy with radiation. The median DFS was 36.7 months. The 3-year DFS and OS was 51.9% (95% CI 36.3-74.1%) and 70.6% (95% CI 57.4-86.8%), respectively. There was no significant difference in DFS and OS among treatment groups. Cox regression analysis showed grade 2-3 tumors and menopause were associated with poor DFS and OS.
CONCLUSION: The DFS and OS in stage III endometrial carcinoma receiving postoperative adjuvant therapy were quite good and were not different among radiation therapy, chemotherapy, and combined treatment groups. The multi-center randomized prospective study was needed to determine the standard modality.

Related: Thailand

Seki T, Yanaihara N, Hirata Y, et al.
Uterine endometrial carcinoma with trophoblastic differentiation: a case report with literature review.
Eur J Gynaecol Oncol. 2014; 35(4):461-4 [PubMed] Related Publications
Choriocarcinoma is categorized as either gestational or nongestational depending on its origin. Nongestational choriocarcinoma originated in the trophoblastic differentiation is a rare but an aggressive tumor. This article reports a nongestational case of a uterine endometrial carcinoma with trophoblastic differentiation. A 54-year-old woman with a history of atypical genital bleeding that underwent semi-radical hysterectomy, bilateral salpingo-oophrectomy, and pelvic lymph nodes dissection. Pathological investigation showed that the tumor had endometrioid adenocarcinoma and choriocarcinomatous components. Although a series of multimodality treatments including craniotomy were performed, she died of aggressive lung and brain metastases one year after the primary surgery.

Rossi A, Forzano L, Romanello I, et al.
Comparison of pelvic masses score (PMS) and Risk of Malignancy Index (RMI 3) in the evaluation of pelvic masses.
Eur J Gynaecol Oncol. 2014; 35(4):421-4 [PubMed] Related Publications
PURPOSE: Ovarian cancer is the fourth cause of death from cancer in women worldwide and the majority of its diagnoses is made in an advanced stage of the disease. Several sonographic scoring systems have been created for a better preoperative discrimination between benign and malignant pelvic masses. The aim of this study was to evaluate the performances of the Risk of the Malignancy Index 3 (RMI 3) and the Pelvic Masses Score (PMS).
MATERIALS AND METHODS: This retrospective study was performed in 55 women admitted to the department of Obstetrics and Gynecology of University of Udine for surgical exploration of pelvic masses between 2009 and 2012. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for both the scores.
RESULTS: PMS showed a sensitivity of 100%, a specificity of 93.8%, a PPV of 70%, and a NPV of 100%, while RMI 3 yielded a sensitivity of 85%, a specificity of 91%, a PPV of 60%, and a NPV of 97.8%.
CONCLUSION: The authors found that, in discriminating between benign and malignant pelvic disease, the PMS method was more reliable than RMI3. PMS is a simple scoring system which can be used in clinical practice.

Related: Ovarian Cancer

Litta P, Di Giuseppe J, Moriconi L, et al.
Predictors of malignancy in endometrial polyps: a multi-institutional cohort study.
Eur J Gynaecol Oncol. 2014; 35(4):382-6 [PubMed] Related Publications
PURPOSE OF INVESTIGATION: The risk of endometrial cancer in women with endometrial polyps (EPs) has been reported to vary between 0.3% and 4.8%. There is a lack of data about the management of asymptomatic women with incidental diagnosis of EPs. In the present study the authors correlated demographic and clinical characteristics with histopathological features of the EPs hysteroscopically removed.
MATERIALS AND METHODS: An observational multi-institutional cohort study was conducted from February 2010 to December 2012 to identify all the premenopausal and postmenopausal women consecutively undergoing hysteroscopic polypectomy. The data of women were reviewed and clinical features were related to histopathologic results.
RESULTS: The patients recruited were 813. The mean age was 52.5 years (range 22-87). The results showed a correlation between older age, high body mass index (BMI) and obesity, postmenopausal state, abnormal uterine bleeding (AUB), hypertension, and risk of malignant EPs. On multivariable analysis, the correlation remained only for age (OR 1.08, 95% CI 1.03 - 1.14) and AUB (OR 3.53, 95% CI 1.87 - 6.65).
CONCLUSION: Older patients in postmenopausal status with AUB, a high BMI, and hypertension are at higher risk for premalignant and malignant polyps. In these patients a surgical approach should be used, consisting in hysteroscopical removing of the polyp.

Günyeli I, Bozkurt KK, Yalçın Y, et al.
Granulosa cell tumor and concurrent endometrial cancer with (18)F-FDG uptake.
Hell J Nucl Med. 2014 May-Aug; 17(2):153-5 [PubMed] Related Publications
The findings and the role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for the diagnosis of ovarian granulosa cell tumor (OG) are described. We present the pre-operative findings of (18)F-FDG PET/CT scan of a case of OG concurrent with endometrium cancer and endometrial hyperplasia, which revealed a 48mm mass demonstrating mild increased metabolic activity on the right ovary. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed. Frozen and paraffin-enbeded sections showed an encapsulated OG. There were few mitoses. There was concurrent atypical endometrial hyperplasia. In conclusion, we reported a case of an encapsulated OG, which showed mild uptake of the (18)F-FDG with concurrent endometrial cancer. There has been only one report of (18)F-FDG findings in primary ovarian granulosa cell tumor, similar to ours.

Saatli B, Yildirim N, Ozay AC, et al.
Synchronous tumors of the female genital tract: a 20-year experience in a single center.
Ginekol Pol. 2014; 85(6):441-5 [PubMed] Related Publications
OBJECTIVE: To evaluate the clinicopathological characteristics and the clinical outcome of synchronous malignant neoplasms of the female reproductive tract.
MATERIAL AND METHODS: Patients who were operated and diagnosed with synchronous malignant tumor of the genital system (n = 25) at the Dokuz Eylul University Department of Obstetrics and Gynecology Gynecologic Oncology Unit between 1992 and 2012 were included into this study. Recurrent, metastatic and metachronously detected tumors were not included. Age at diagnosis, parity menopausal status, hormone use, presenting sign or symptoms and the clinical outcomes were evaluated.
RESULTS: 20 of 25 patients had endometrial-ovarian cancer. The mean age at diagnosis was 53,6 years. The most common presenting symptom was abnormal uterine bleeding. The median follow-up duration for all patients was 69 months. Overall survival for all patients was 87 months and 81 months for patients with endometrial-ovarian cancer 5-year survival rate was 73% for all patients and 68% for patients with endometrial-ovarian cancer.
CONCLUSIONS: Endometrial-ovarian cancer togetherness is the most common in synchronous gynecologic malignancies. They occur at a younger age and have more favorable prognosis than metastatic primary gynecologic tumors.

Related: Gynacological Cancers Ovarian Cancer

Chui MH, Ryan P, Radigan J, et al.
The histomorphology of Lynch syndrome-associated ovarian carcinomas: toward a subtype-specific screening strategy.
Am J Surg Pathol. 2014; 38(9):1173-81 [PubMed] Related Publications
Women with Lynch syndrome (LS) are at increased risk for the development of epithelial ovarian cancer (OC). Analogous to previous studies on BRCA1/2 mutation carriers, there is evidence to suggest a histotype-specific association in LS-associated OCs (LS-OC). Whereas the diagnosis of high-grade serous carcinoma is an indication for BRCA1/2 germline testing, in contrast, there are no screening guidelines in place for triaging OC patients for LS testing based on histotype. We performed a centralized pathology review of tumor subtype on 20 germline mutation-confirmed LS-OCs, on the basis of morphologic assessment of hematoxylin and eosin-stained slides, with confirmation by immunohistochemistry when necessary. Results from mismatch-repair immunohistochemistry (MMR-IHC) and microsatellite instability (MSI) phenotype status were documented, and detailed pedigrees were analyzed to determine whether previously proposed clinical criteria would have selected these patients for genetic testing. Review of pathology revealed all LS-OCs to be either pure endometrioid carcinoma (14 cases), mixed carcinoma with an endometrioid component (4 cases), or clear cell carcinoma (2 cases). No high-grade or low-grade serous carcinomas or mucinous carcinomas of intestinal type were identified. Tumor-infiltrating lymphocytes were prominent (≥40 per 10 high-powered fields) in 2 cases only. With the exception of 1 case, all tumors tested for MMR-IHC or MSI had an MMR-deficient phenotype. Within this cohort, 50%, 55%, 65%, and 85% of patients would have been selected for genetic workup by Amsterdam II, revised Bethesda Guidelines, SGO 10% to 25%, and SGO 5% to 10% criteria, respectively, with <60% of index or sentinel cases detected by any of these schemas. To further support a subtype-driven screening strategy, MMR-IHC reflex testing was performed on all consecutive non-serous OCs diagnosed at 1 academic hospital over a 2-year period; MMR deficiency was identified in 10/48 (21%) cases, all with endometrioid or clear cell histology. We conclude that there is a strong association between endometrioid and clear cell ovarian carcinomas and hereditary predisposition due to MMR gene mutation. These findings have implications for the role of tumor subtype in screening patients with OC for further genetic testing and support reflex MMR-IHC and/or MSI testing for newly diagnosed cases of endometrioid or clear cell ovarian carcinoma.

Related: Canada Cancer Screening and Early Detection Ovarian Cancer

Cho H, Nam BH, Kim SM, et al.
A phase 2 trial of radiation therapy with concurrent paclitaxel chemotherapy after surgery in patients with high-risk endometrial cancer: a Korean Gynecologic Oncologic Group study.
Int J Radiat Oncol Biol Phys. 2014; 90(1):140-6 [PubMed] Related Publications
PURPOSE: A phase 2 study was completed by the Korean Gynecologic Oncologic Group to evaluate the efficacy and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with high-risk endometrial cancer.
METHODS AND MATERIALS: Pathologic requirements included endometrial endometrioid adenocarcinoma stages III and IV. Radiation therapy consisted of a total dose of 4500 to 5040 cGy in 5 fractions per week for 6 weeks. Paclitaxel 60 mg/m(2) was administered once weekly for 5 weeks during radiation therapy.
RESULTS: Fifty-seven patients were enrolled between January 2006 and March 2008. The median follow-up time was 60.0 months (95% confidence interval [CI], 51.0-58.2). All grade 3/4 toxicities were hematologic and usually self-limited. There was no life-threatening toxicity. The cumulative incidence of intrapelvic recurrence sites was 1.9% (1/52), and the cumulative incidence of extrapelvic recurrence sites was 34.6% (18/52). The estimated 5-year disease-free and overall survival rates were 63.5% (95% CI, 50.4-76.5) and 82.7% (95% CI, 72.4-92.9), respectively.
CONCLUSIONS: Concurrent chemoradiation with weekly paclitaxel is well tolerated and seems to be effective for high-risk endometrioid endometrial cancers. This approach appears reasonable to be tested for efficacy in a prospective, randomized controlled study.

Related: Paclitaxel

Fournier A, Dossus L, Mesrine S, et al.
Risks of endometrial cancer associated with different hormone replacement therapies in the E3N cohort, 1992-2008.
Am J Epidemiol. 2014; 180(5):508-17 [PubMed] Related Publications
We assessed whether different oral progestogens in hormone replacement therapy may differentially affect the risk of endometrial cancer, using data from the Etude Epidémiologique auprès de femmes de l'Education Nationale (E3N), a French cohort study (1992-2008). Hazard ratios and their confidence intervals were derived from Cox models. Among 65,630 postmenopausal women (mean follow-up: 10.8 years), 301 endometrial cancers occurred. Compared with never use, ever use of estrogen + micronized progesterone was associated with an increased risk of endometrial cancer (hazard ratio (HR) = 1.80, 95% confidence interval (CI): 1.38, 2.34) that was significantly more marked with longer duration of use (for ≤5 years, HR = 1.39 (95% CI: 0.99, 1.97); for >5 years, HR = 2.66 (95% CI: 1.87, 3.77)). Although use of estrogen + dydrogesterone was not associated overall with endometrial cancer risk (HR = 1.05, 95% CI: 0.76, 1.45), there was a significantly increased risk with long-term use compared with never use (for >5 years, HR = 1.69, 95% CI: 1.06, 2.70). Users of preparations containing other progesterone derivatives or a norsteroid derivative were not at significantly increased risk (HR = 0.79 (95% CI: 0.60, 1.05) and HR = 1.30 (95% CI: 0.85, 1.99), respectively). In conclusion, micronized progesterone and, to a lesser extent, dydrogesterone at the doses used in France may not be sufficient to prevent estrogen-induced endometrial cancers.

Nevadunsky NS, Van Arsdale A, Strickler HD, et al.
Obesity and age at diagnosis of endometrial cancer.
Obstet Gynecol. 2014; 124(2 Pt 1):300-6 [PubMed] Related Publications
OBJECTIVE: Obesity is an established risk factor for development of endometrial cancer. We hypothesized that obesity might also be associated with an earlier age at endometrial cancer diagnosis, because mechanisms that drive the obesity-endometrial cancer association might also accelerate tumorigenesis.
METHODS: A retrospective chart review was conducted of all cases of endometrial cancer diagnosed from 1999 to 2009 at a large medical center in New York City. The association of body mass index (BMI) with age at endometrial cancer diagnosis, comorbidities, stage, grade, and radiation treatment was examined using analysis of variance and linear regression. Overall survival by BMI category was assessed using Kaplan-Meier method and the log-rank test.
RESULTS: A total of 985 cases of endometrial cancer were identified. The mean age at endometrial cancer diagnosis was 67.1 years (±11.9 standard deviation) in women with a normal BMI, whereas it was 56.3 years (±10.3 standard deviation) in women with a BMI greater than 50. Age at diagnosis of endometrioid-type cancer decreased linearly with increasing BMI (y=67.89-1.86x, R=0.049, P<.001). This association persisted after multivariable adjustment (R=0.181, P<.02). A linear association between BMI and age of nonendometrioid cancers was not found (P=.12). There were no differences in overall survival by BMI category.
CONCLUSIONS: Obesity is associated with earlier age at diagnosis of endometrioid-type endometrial cancers. Similar associations were not, however, observed with nonendometrioid cancers, consistent with different pathways of tumorigenesis.

Yost KJ, Cheville AL, Al-Hilli MM, et al.
Lymphedema after surgery for endometrial cancer: prevalence, risk factors, and quality of life.
Obstet Gynecol. 2014; 124(2 Pt 1):307-15 [PubMed] Related Publications
OBJECTIVE: To estimate lower extremity lymphedema prevalence in patients surgically treated for endometrial cancer, identify predictors of lymphedema, and evaluate the effects of lymphedema on quality of life.
METHODS: One thousand forty-eight consecutive patients who were operated on between 1999 and 2008 at the Mayo Clinic were mailed a survey, which included our validated 13-item lymphedema screening questionnaire and two validated quality-of-life measures. Logistic regression models were fit to identify factors associated with prevalent lymphedema; a multivariable model was obtained using stepwise and backward variable selection methods. The relationship between lymphedema and obesity with each quality-of-life score was evaluated separate multivariable linear models.
RESULTS: There were 591 responders (56%) after exclusions. Our questionnaire revealed a previous self-reported lymphedema diagnosis in 103 (17%) patients and identified undiagnosed lymphedema in 175 (30%) (overall prevalence 47.0%, median 6.2 years follow-up). Lymphedema prevalence in patients treated with hysterectomy alone compared with lymphadenectomy was 36.1% and 52.3%, respectively (attributable risk 23%). Lymphedema risk was not associated with the number of nodes removed or the extent of lymphadenectomy after adjusting for other factors. On multivariable analysis, higher body mass index, congestive heart failure, performance of lymphadenectomy, and radiation therapy were associated with prevalent lymphedema. Multiple quality-of-life scores were worse in women with lymphedema.
CONCLUSION: The attributable risk of developing lower extremity lymphedema was 23% for patients with endometrial cancer who underwent lymphadenectomy compared with hysterectomy alone with an overall prevalence of 47%. Lymphedema was associated with reductions in multiple quality-of-life domains.

Sauer CM, Chatterjee S, Israel GM, Schwartz PE
Endometrial adenocarcinoma presenting as a hematotrachelos.
Obstet Gynecol. 2014; 124(2 Pt 2 Suppl 1):448-51 [PubMed] Related Publications
BACKGROUND: Hematotrachelos, distension of the uterine cervix with accumulated blood, is an extremely rare condition resulting from a congenital anomaly or an acquired condition. We present a case in which an acquired hematotrachelos was the presenting sign of endometrial cancer.
CASE: An asymptomatic 66-year-old woman was found to have a bulging cervix during a well-woman visit. Further workup revealed a hematotrachelos and an underlying endometrial adenocarcinoma. She was treated with surgery and adjuvant radiotherapy.
CONCLUSION: A hematotrachelos, although rare, can prevent vaginal bleeding, which is often the earliest symptom of a uterine malignancy. This case report illustrates the potential importance of the pelvic examination as part of the well-woman physical examination, because it led to the discovery of early-stage endometrial cancer.

Ulm MA, Robins DB, Thorpe EM, Reed ME
Endometrioid adenocarcinoma in an extrauterine adenomyoma.
Obstet Gynecol. 2014; 124(2 Pt 2 Suppl 1):445-8 [PubMed] Related Publications
BACKGROUND: Focal involvement by endometrioid adenocarcinoma in an extrauterine adenomyoma in a patient with stage 1 endometrioid adenocarcinoma presented a unique problem in staging and management of extrauterine endometrial cancer.
CASE: A 49-year-old white woman, gravida 0, referred for endometrioid adenocarcinoma was found to have an extrauterine adenomyoma involved with endometrioid adenocarcinoma in the inguinal canal after surgical staging. The endometrioid adenocarcinoma involving the extrauterine adenomyoma was low-grade and noninvasive, representing an embryological anomaly transformed into endometrioid adenocarcinoma by unopposed estrogen. Stage 1A, grade 2 endometrioid adenocarcinoma was diagnosed and observed.
CONCLUSION: Stage 1 endometrioid adenocarcinoma with concurrent, noninvasive, focal involvement in an extrauterine adenomyoma represents a secondary site and does not alter disease stage.

Bell JG, Patterson DM, Klima J, et al.
Outcomes of patients with low-risk endometrial cancer surgically staged without lymphadenectomy based on intra-operative evaluation.
Gynecol Oncol. 2014; 134(3):505-9 [PubMed] Related Publications
OBJECTIVE: The objective of the study was to evaluate clinical outcomes in patients with stage I endometrial cancer undergoing surgical management without lymphadenectomy based on intra-operative assessment for low-risk disease.
METHODS: Between 2000 and 2009, a total of 179 patients were surgically staged without lymphadenectomy for low-risk stage I endometrial cancer. Low-risk cancer was defined by intra-operative criteria based on both gross and frozen tissue microscopic evaluation: 1) G1 or G2 endometrioid histology; 2) myoinvasion <50%; 3) no cervical disease, and 4) no intra-abdominal metastasis. Records were reviewed for postoperative complications, pathological diagnoses, adjuvant radiation treatment, cancer recurrence, and mortality.
RESULTS: Morbidity, cancer recurrence, and disease-specific mortality were low. Postoperative complications occurred in 5 patients (2.8%). Nine patients (5.0%) were offered adjuvant radiation for higher risk disease diagnosed on final pathology. Radiation morbidity was minimal: grade 1 vaginal toxicity in 2 patients. Three patients (1.7%) experienced recurrent cancer with mean time to recurrence of 43.7 months. Five year overall survival was 95.8%. The five year probability of disease-specific death was 1.1%.
CONCLUSION: In an institution with reliable capability of pathological frozen tissue diagnosis, omission of lymph node dissection is a reasonable option in the surgical management of those patients with low-risk disease diagnosed by intra-operative factors.

Tateo S, Nozza A, Del Pezzo C, Mereu L
Robotic single-site pelvic lymphadenectomy.
Gynecol Oncol. 2014; 134(3):631 [PubMed] Related Publications
OBJECTIVE: To examine the feasibility of performing pelvic lymphadenectomy with robotic single site approach. Recent papers described the feasibility of robotic-single site hysterectomy [1-3] for benign and malign pathologies but only with the development of new single site 5mm instruments as the bipolar forceps, robotic single site platform can be safely utilized also for lymphadenectomy.
METHODS: A 65 year-old, multiparous patient with a body mass index of 22.5 and diagnosed with well differentiated adenocarcinoma of the endometrium underwent a robotic single-site peritoneal washing, total hysterectomy, bilateral adnexectomy and pelvic lymphadenectomy. The procedure was performed using the da Vinci Si Surgical System (Intuitive Surgical, Sunnyvale, CA) through a single 2,5 cm umbilical incision, with a multi-channel system and two single site robotic 5mm instruments. A 3-dimensional, HD 8.5mm endoscope and a 5mm accessory instrument were also utilized.
RESULTS: Type I lymphonodes dissection for external iliac and obturator regions was performed [4]. Total operative time was 210 min; incision, trocar placement and docking time occurring in 12 min. Total console time was 183 min, estimated blood loss was 50 ml, no intra-operative or post-operative complications occurred. Hospital discharge occurred on post operative day 2 and total number of lymphnodes removed was 33. Difficulties in term of instrument's clashing and awkward motions have been encountered.
CONCLUSION: Robotic single-site pelvic lymphadenectomy using bipolar forceps and monopolar hook is feasible. New developments are needed to improve surgical ergonomics and additional studies should be performed to explore possible benefits of this procedure.

Bruchim I, Sarfstein R, Reiss A, et al.
IGF1R tyrosine kinase inhibitor enhances the cytotoxic effect of methyl jasmonate in endometrial cancer.
Cancer Lett. 2014; 352(2):214-9 [PubMed] Related Publications
The present study evaluated the cytotoxic activity of methyl jasmonate (MJ) in endometrial cancer cells and examined the hypothesis that the apoptotic and anti-proliferative actions of MJ in these cell lines can be enhanced by co-targeting the insulin-like growth factor-1 receptor (IGF1R) signaling pathway. MJ had a potent pro-apoptotic effect and exhibited significant toxicity in all cell lines tested. MJ in combination with NVP-AEW541, a selective IGF1R tyrosine kinase inhibitor, had significantly increased cytotoxicity. MJ decreased IGF1R phosphorylation, however, it enhanced AKT phosphorylation and abolished the anti-apoptotic effect of IGF1. These findings suggest that combined IGF1R inhibitor and MJ administration may constitute an attractive modality for treating endometrial cancer.

Related: Apoptosis AKT1 IGF1R

Wik E, Trovik J, Kusonmano K, et al.
Endometrial Carcinoma Recurrence Score (ECARS) validates to identify aggressive disease and associates with markers of epithelial-mesenchymal transition and PI3K alterations.
Gynecol Oncol. 2014; 134(3):599-606 [PubMed] Related Publications
PURPOSE: Our previously reported 29-gene expression signature identified an aggressive subgroup of endometrial cancer patients with PI3K activation. We here wanted to validate these findings by independent patient series.
PATIENTS AND METHODS: The 29-gene expression signature was assessed in fresh frozen tumor tissue from 280 primary endometrial carcinomas (three independent cohorts), 19 metastatic lesions and in 333 primary endometrial carcinomas using TCGA data, and expression was related to clinico-pathologic features and survival. The 29-gene signature was assessed by real-time quantitative PCR, DNA oligonucleotide microarrays, or RNA sequencing. PI3K alterations were assessed by immunohistochemistry, DNA microarrays, DNA sequencing, SNP arrays or fluorescence in situ hybridization. A panel of markers of epithelial-mesenchymal transition (EMT) was also correlated to the 29-gene signature score.
RESULTS: High 29-gene Endometrial Carcinoma Recurrence Score (ECARS) values consistently validated to identify patients with aggressive clinico-pathologic phenotype and reduced survival. Within the presumed favorable subgroups of low grade, endometrioid tumors confined to the uterus, high ECARS still predicted a poor prognosis. The score was higher in metastatic compared to primary lesions (P<0.001) and was significantly associated with potential measures of PI3K activation, markers of EMT and vascular invasion as an indicator of metastatic spread (all P<0.001).
CONCLUSIONS: ECARS validates to identify aggressive endometrial carcinomas in multiple, independent patients cohorts. The higher signature score in metastatic compared to primary lesions, and the potential link to PI3K activation and EMT, support further studies of ECARS in relation to response to PI3K and EMT inhibitors in clinical trials of metastatic endometrial carcinoma.

Fan JT, Li MJ, Shen P, et al.
Serum and tissue level of YKL-40 in endometrial cancer.
Eur J Gynaecol Oncol. 2014; 35(3):304-8 [PubMed] Related Publications
OBJECTIVE: Serum YKL-40 level is elevated in patients with several malignancies. This study was designed to assess the correlation between serum YKL-40 and the corresponding tissue expression in endometrial cancer (EC).
MATERIALS AND METHODS: Preoperative serum levels of YKL-40 were measured by enzyme-linked immunosorbent assay (ELISA) from 41 patients with EC, 27 patients with uterine myoma, and 30 healthy women. YKL-40 protein expression in tissue was determined by immunohistochemistry for patients with EC and patients with uterine myoma.
RESULTS: Median preoperative serum YKL-40 level was 157.2 microg/l (range 76.0 - 301.2) in EC compared with 86.6 microg/l (range 69.3 - 191.1) in uterine myoma, and 86.2 microg/l (range 52.1 - 201.1) in healthy women (p < 0.05). Of 41 patients with EC, 26 patients with elevated serum YKL-40 level statistically differed from the remaining 15 patients with normal serum YKL-40 level with respect to FIGO Stage, tumor grade, washing cytology, and serum CA125 (p < 0.05). In multivariate analysis, elevated serum YKL-40 significantly correlated with FIGO stage (p < 0.05) and tumor grade (p < 0.01). The percentage of positive YKL-40 tissue staining was higher in EC patients (34.1%, 14/41) than in uterine myoma patients (11.1%, 3/27) (p < 0.05) and was lower than that of elevated serum levels in EC (26/41, 63.4%) (p < 0.05).
CONCLUSIONS: The elevated preoperative serum YKL-40 is related to stage and histologic grade of EC. The discordance between serum and tissue level of YKL-40 in EC indicates intrauterine tumor may not be the only source of serum YKL-40.

Togami S, Hori S, Kamio M, et al.
Clinical usefulness of concentrated ascites reinfusion therapy (CART) for gynecological cancer patients with refractory massive ascites due to cancerous peritonitis.
Eur J Gynaecol Oncol. 2014; 35(3):301-3 [PubMed] Related Publications
PURPOSE: Cell-free and concentrated ascites reinfusion therapy (CART) is intended to treat patients by ultrafiltration and reinfusion of their refractory ascites. In the CART system, bacteria and cancer cells in removed massive ascites are filtrated. Then, water is removed in the condenser, resulting in a higher protein concentration. The purpose of this study was to assess the clinical usefulness of CART in the treatment of refractory massive ascites in patients with cancerous peritonitis.
MATERIALS AND METHODS: CART was performed 13 times in four patients with ovarian and endometrial cancer.
RESULTS: Autologous protein with a higher concentration was intravenously administered. The amount of aspirated and condensed ascites was 3,190 +/- 1,086 ml (975 4,500 ml) and 538 +/- 249 ml (100 - 860 ml), respectively. Condensed albumin, albumin concentration, and concentration time were 43.2 +/- 25.8 g, 8.2 +/- 3.3 g/dl, and 73.3 +/- 24.8 min (28 - 122 min), respectively. CART was effective in maintaining serum albumin concentrations, and it is possible to repeat infusion. During CART, patients performance status was 1-2 and vital signs were stable except for mild elevations in body temperature. Daily life was maintained without serious side-effects.
CONCLUSIONS: The use of CART for gynecological cancer patients with refractory massive ascites due to cancerous peritonitis contributes to improvements in quality of life and relief of symptoms. With autologous infusion of condensed ascites, patients can avoid infection, allergic reactions, and administration of expensive blood products.

Related: Ovarian Cancer

Matoda M, Omatsu K, Yamamoto A, et al.
Importance of platinum-free interval in second-line chemotherapy for advanced or recurrent endometrial cancer.
Eur J Gynaecol Oncol. 2014; 35(3):224-9 [PubMed] Related Publications
PURPOSE: To investigate the effectiveness of platinum-based combination chemotherapy as second-line chemotherapy for patients with advanced or recurrent endometrial cancer treated initially by platinum-based combination chemotherapy.
MATERIALS AND METHODS: Subjects were patients who had received platinum-based combination chemotherapy as second-line chemotherapy: 56 patients with recurrent disease who had previously received postoperative adjuvant platinum-based combination chemotherapy (Category 1) and 21 patients who had received first-line chemotherapy but not adjuvant chemotherapy for advanced or recurrent disease (Category 2). Patients' records were searched for the response to second-line chemotherapy and survival, particularly in relation to the platinum-free interval (PFI).
RESULTS: APFI over 12 months was a predictor of response (64.7%) and overall survival time (23 months) in Category 1 patients. A PFI of less than three months was a negative predictor of response (0%) and overall survival (nine months) in Category 2 patients.
CONCLUSION: Platinum-based combination chemotherapy appears to be effective as second-line chemotherapy for endometrial cancer if the PFI is sufficiently long.

Tirmazy SH, Barthakur U, El-Modir A, et al.
Chemotherapy for advanced endometrial cancer with carboplatin and epirubicin.
Anticancer Res. 2014; 34(7):3793-8 [PubMed] Related Publications
UNLABELLED: Endometrial cancer is the most common gynecological cancer in the Western world. In early-stage disease, surgery remains the mainstay of treatment. Adjuvant pelvic radiotherapy reduces the risk of pelvic recurrence, however, without improvement in overall survival. The aim of the present study was to assess the efficacy and toxicity of carboplatin and epirubicin combination chemotherapy for patients with advanced and high-risk endometrial cancer.
PATIENTS AND METHODS: Between 1999 and 2007, 43 patients with endometrial cancer were treated with carboplatin and epirubicin. Two groups were identified: Group 1 (n=34) included patients with stage III endometrial cancer receiving adjuvant chemotherapy; and group 2 included those with metastatic endometrial cancer (n=9).
RESULTS: After a median follow-up of 37 months, disease in 19 patients had progressed/relapsed (12 patients from group 1; 7 from group 2) and 23 patients had died (15 from group 1; 8 from group 2). The median time-to-progression was 62 months and median overall survival was 64 months. The median survival for patients in group 1 was 69 months and for those in group 2 was 22 months. Ten patients (27.9%) experienced grade 3 or 4 toxicities. There were no cases of treatment-related cardiac failure or neuropathy.
CONCLUSION: Cisplatin, carboplatin, anthracyclines and taxanes are the most active agents in endometrial cancer. Combination chemotherapy leads to better progression-free survival and overall survival, however, this is at the expense of increased toxicity. RESULTS from our study show that the combination of carboplatin and epirubicin is an effective alternative regimen for patients with advanced endometrial cancer. In addition, treatment-related toxicity is minimal when compared to anthracyclines and platinum agents. There is a particular advantage of this regimen over taxane-based regimens, including minimal neuropathy, less use of steroids and low risk of allergic reaction and alopecia.

Related: Carboplatin Epirubicin

Elshaikh MA, Yashar CM, Wolfson AH, et al.
ACR appropriateness Criteria® advanced stage endometrial cancer.
Am J Clin Oncol. 2014; 37(4):391-6 [PubMed] Related Publications
OBJECTIVES: Patients with advanced stage endometrial carcinoma constitute a heterogeneous group of patients with different stages, tumor histologic types, and involved sites. Hysterectomy, bilateral salpingo-ophorectomy, and surgical staging are the cornerstone of surgical management in these patients. The optimal adjuvant therapy is yet to be established. An expert panel was convened to reach consensus on the most appropriate management options in this group of patients.
METHODS: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
RESULTS: Four clinical variants were developed to address common scenarios in the management of women with advanced-stage endometrial carcinoma. Group members reached consensus on the appropriateness of specific evaluation and treatment approaches with numerical ratings.
CONCLUSIONS: In combining available medical literature and expert opinions, this manuscript may serve as an aid for other practitioners in the appropriate management of women with advanced-stage endometrial carcinoma.

Laskov I, Drudi L, Beauchamp MC, et al.
Anti-diabetic doses of metformin decrease proliferation markers in tumors of patients with endometrial cancer.
Gynecol Oncol. 2014; 134(3):607-14 [PubMed] Related Publications
BACKGROUND: Metformin has been associated with reduced cancer risk. The mechanisms underlying this cancer protective effect remain unknown.
METHODS: "Window of opportunity" study of metformin in women with operable endometrial cancer (EC). Eleven newly diagnosed, untreated, non-diabetic patients with EC received metformin 500 mg tid from diagnostic biopsy to surgery. Fasting plasma insulin, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 1 (IGFBP-1) and insulin-like growth factor binding protein 7 (IGFBP-7) measurements were taken before and after metformin treatment. Ki-67, pAMPK, and pS6 immunohistochemistry staining was performed on the endometrial cancer before and after metformin treatment and was compared to a control group of 10 women with EC who did not receive metformin.
RESULTS: Metformin was administered for a mean of 36.6 days. None of the patients suffered side effects requiring withdrawal from the study. The study group comprised 8 patients with endometrioid EC, and 3 non-endometrioid EC, with a mean follow-up time of 57 months. Mean plasma insulin (p=0.0005), IGF-1 (p=0.001), and IGFBP-7 (p=0.0098) were significantly reduced after metformin treatment. A clear reduction in ki-67 and pS6 expression was observed by both conventional light microscope analysis and digital image analysis with a significant mean reduction in percentage of cells staining for ki-67 (9.7%, P=0.02) and pS6 (31%, P=0.03). In the non-treated control group expression was similar between the biopsy and the surgical specimens.
CONCLUSIONS: This pilot trial presents biological evidence consistent with anti-proliferative effects of metformin in women with EC in the clinical setting.

Carmona R, Gulaya S, Murphy JD, et al.
Validated competing event model for the stage I-II endometrial cancer population.
Int J Radiat Oncol Biol Phys. 2014; 89(4):888-98 [PubMed] Related Publications
PURPOSE/OBJECTIVES(S): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification.
METHODS AND MATERIALS: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality.
RESULTS: In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification.
CONCLUSION: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification.

Related: USA

Boers-Sonderen MJ, van Herpen CM, van der Graaf WT, et al.
Correlation of toxicity and efficacy with pharmacokinetics (PK) of pegylated liposomal doxorubicin (PLD) (Caelyx®).
Cancer Chemother Pharmacol. 2014; 74(3):457-63 [PubMed] Related Publications
PURPOSE: Pegylated liposomal doxorubicin (PLD) is used to treat patients with breast and gynecological cancers. In order to optimize treatment with PLD, we assessed the prognostic and predictive factors for efficacy of PLD.
METHODS: Seventeen patients treated with PLD 30 or 40 mg/m(2) underwent pharmacokinetic sampling during the first cycle of treatment. PLD exposure was calculated. An univariate analysis was performed with the variables: hand-foot syndrome, mucositis, rash, neutropenia, age, tumor type, number of previous therapies, ECOG performance status and progression-free survival (PFS). Candidate variables with p ≤ 0.1 were selected for the multivariate analysis.
RESULTS: Based on the results of the multivariate analysis, the PLD exposure (log AUC) was higher in patients who experienced rash (p = 0.002) and mucositis (p = 0.001) compared to those who did not have these adverse events. The development of hand-foot syndrome was significantly related to a lower risk of disease progression (HR 0.1; 95 % CI 0.02-0.64). Patients with an ECOG status of 0 had a longer PFS than the patients with an ECOG status of 1 (HR 5.4; 95 % CI 1.3-22.8). Moreover, PLD exposure (ln AUC) was also positively related to PFS (HR 0.001; 95 % CI 0.00-0.42).
CONCLUSIONS: The extent of the exposure to PLD was correlated with more adverse events and longer PFS. This has important clinical implications, since dose reductions or interruptions might thus negatively affect treatment outcomes. More attention should be paid to preventive and supportive measures of adverse events of PLD to keep the exposure to PLD as high as possible.

Related: Breast Cancer Doxorubicin Ovarian Cancer Liposomal Doxorubicin Temsirolimus (Torisel)

Chiang S, Soslow RA
Updates in diagnostic immunohistochemistry in endometrial carcinoma.
Semin Diagn Pathol. 2014; 31(3):205-15 [PubMed] Related Publications
Diagnostic difficulty in the morphologic assessment of endometrial carcinomas may arise in pathology practice. Challenges in tumor classification exist especially in the setting of high-grade carcinomas. These include FIGO grade 3 endometrioid, serous, clear cell, and undifferentiated carcinomas, in addition to carcinomas of mixed cell type and those exhibiting ambiguous morphologic features. This comprehensive review details key morphologic and immunophenotypic features of prototypic endometrial carcinomas, including a description of both well-established and novel immunohistochemical markers in the evaluation of these tumors. It also provides recommendations regarding prudent use of these ancillary techniques in distinguishing between various histologic subtypes of endometrial carcinoma that frequently result in persistent diagnostic problems.

Djordjevic B, Broaddus RR
Role of the clinical pathology laboratory in the evaluation of endometrial carcinomas for Lynch syndrome.
Semin Diagn Pathol. 2014; 31(3):195-204 [PubMed] Article available free on PMC after 01/05/2015 Related Publications
Molecular diagnostic testing of endometrial carcinomas in the pathology laboratory has recently emerged as a key component of the clinical evaluation of Lynch syndrome in many centers. Testing modalities involve immunohistochemical and PCR-based analyses. This article outlines the routine application of these analyses, provides a practical guide for troubleshooting some of the common technical issues related to their performance, and reviews common pitfalls in their interpretation. Discrepancies between tissue testing and genetic testing results are discussed in the context of the current understanding of endometrial cancer biology. The merits of universal versus targeted tissue testing based on clinical patient history and histological tumor appearance are also addressed.

Slaughter KN, Frumovitz M, Schmeler KM, et al.
Minimally invasive surgery for endometrial cancer: does operative start time impact surgical and oncologic outcomes?
Gynecol Oncol. 2014; 134(2):248-52 [PubMed] Related Publications
OBJECTIVE: Recent literature in ovarian cancer suggests differences in surgical outcomes depending on operative start time. We sought to examine the effects of operative start time on surgical outcomes for patients undergoing minimally invasive surgery for endometrial cancer.
METHODS: A retrospective review was conducted of patients undergoing minimally invasive surgery for endometrial cancer at a single institution between 2000 and 2011. Surgical and oncologic outcomes were compared between patients with an operative start time before noon and those with a surgical start time after noon.
RESULTS: A total of 380 patients were included in the study (245 with start times before noon and 135 with start times after noon). There was no difference in age (p=0.57), number of prior surgeries (p=0.28), medical comorbidities (p=0.19), or surgical complexity of the case (p=0.43). Patients with surgery starting before noon had lower median BMI than those beginning after noon, 31.2 vs. 35.3 respectively (p=0.01). No significant differences were observed for intraoperative complications (4.4% of patients after noon vs. 3.7% of patients before noon, p=0.79), estimated blood loss (median 100 cc vs. 100 cc, p=0.75), blood transfusion rates (7.4% vs. 8.2%, p=0.85), and conversion to laparotomy (12.6% vs. 7.4%, p=0.10). There was no difference in operative times between the two groups (198 min vs. 216.5 min, p=0.10). There was no association between operative start time and postoperative non-infectious complications (11.9% vs. 11.0%, p=0.87), or postoperative infections (17.8% vs. 12.3%, p=0.78). Length of hospital stay was longer for surgeries starting after noon (median 2 days vs. 1 day, p=0.005). No differences were observed in rates of cancer recurrence (12.6% vs. 8.8%, p=0.39), recurrence-free survival (p=0.97), or overall survival (p=0.94).
CONCLUSION: Our results indicate equivalent surgical outcomes and no increased risk of postoperative complications regardless of operative start time in minimally invasive endometrial cancer staging, despite longer length of hospital stay for surgeries beginning after noon.

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