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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Menu: Endometrial (Uterus) Cancer

Information for Patients and the Public
Information for Health Professionals / Researchers
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).

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

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

Showkat MS, Nabi S, Khondker L, et al.
Role of transvaginal sonography in the detection of endometrial carcinoma.
Bangladesh Med Res Counc Bull. 2013; 39(2):80-5 [PubMed] Related Publications
Transvagival sonography is superior to transabdominal sonography in most cases of pelvic pathology. Objective of this study is to evaluate the clinical usefulness of transvaginal ultrasonography (TVS) in pre, peri and post menopausal women suspected to have endometrial carcinoma. This cross sectional study was done with 40 patients who are clinically suspected having thickened endometrium. The study was carried out January 2007 to November 2008 for a period of two years. The patients having endometrial carcinoma diagnosed by TVS was correlated with histopathological diagnosis following collection of the report from the respective cases. Of total 40 cases, 2 (5.0%) cases were endometrial carcinoma and 38 (95.0%) were negative for endometrial carcinoma respectively in TVS findings. On the other hand 3 (7.5%) cases were endometrial carcinoma and 37 (92.5%) cases were negative for endometrial carcinoma in histopathological findings. The validity of TVS in diagnosis of endometrial carcinoma were studied by calculating sensitivity, specificity, accuracy, positive predictive value and negative predictive value, which were 67 percent, 100 percent, 98 percent, 100 percent and 97 percent respectively. As the TVS findings of the present study correlated well with the histopathology findings and the validity test values were higher than observed by others, it can be concluded that TVS is sensitive and accurate modality in the evaluation of endometrial carcinoma.

Bats AS, Blons H, Narjoz C, et al.
Microsatellite instability analysis in uterine cavity washings to detect endometrial cancer in Lynch syndrome.
Anticancer Res. 2014; 34(6):3211-5 [PubMed] Related Publications
AIM: To assess the feasibility of Microsatellite Instability (MSI) analysis in uterine cavity washings for detecting endometrial cancer in Lynch syndrome.
MATERIALS AND METHODS: This was a proof-of-concept study in Lynch syndrome patients, scheduled for hysterectomy. At the beginning of surgical procedure, uterine cavity washings were performed, and sent for MSI analysis. Pathological examination of the uterus was associated with mismatch repair protein expression and MSI analysis.
RESULTS: Nine patients were included in the study. Uterine cavity washings were feasible and interpretable in all cases. Final histological report identified 2 endometrial cancers and 7 benign specimens. There was no atypical hyperplasia. Sensitivity, specificity, positive predictive value, and negative predictive value of MSI analysis in uterine washings reached 100% in all cases. Concordance of MSI presence or absence was absolute between uterine washings and final histology.
CONCLUSION: MSI analysis in uterine cavity washings may be a promising screening tool for Lynch syndrome-associated endometrial cancer diagnosis.

Quan P, Moinfar F, Kufferath I, et al.
Effects of targeting endometrial stromal sarcoma cells via histone deacetylase and PI3K/AKT/mTOR signaling.
Anticancer Res. 2014; 34(6):2883-97 [PubMed] Related Publications
AIM: Endometrial stromal sarcoma (ESS) is a rare gynecological mesenchymal malignancy with only few therapeutic options. This study aimed to investigate the efficacy of the histone deacetylase (HDAC) inhibitor suberanilohydroxamic acid (SAHA) combined with inhibitors of the phosphoinositid-3-Kinase (PI3K) pathway in ESS therapy.
MATERIALS AND METHODS: The effects of SAHA combined with inhibitor of PI3K (LY294002, LY), mammalian target of rapamycin mTOR (rapamycin), and their combination on cell growth and the PI3K pathway in two ESS cell lines (ESS-1 and MES-SA) and one non-neoplastic cell line HESC, were investigated.
RESULTS: SAHA reduced growth of the three cell lines by inhibiting protein kinase B AKT and mTOR/p70S6K cascade activation. SAHA combined with LY or rapamycin, or both, synergistically reduced p-p70S6K and p-4E-BP1 levels. SAHA combined with LY and rapamycin led to the strongest growth inhibition and slowest growth recovery among the combination treatments.
CONCLUSION: SAHA combined with inhibition of PI3K and mTOR could represent an efficient therapy option for patients with ESS.

Related: Apoptosis AKT1 Signal Transduction

Shao R, Li X, Feng Y, et al.
Direct effects of metformin in the endometrium: a hypothetical mechanism for the treatment of women with PCOS and endometrial carcinoma.
J Exp Clin Cancer Res. 2014; 33:41 [PubMed] Free Access to Full Article Related Publications
Although a number of in vitro studies have demonstrated the antiproliferative, anti-invasive, and antimetastatic effects of metformin in multiple cancer cell types, its cellular and molecular mechanisms of anti-cancer action in the endometrium of women with polycystic ovary syndrome (PCOS) have not yet been fully elucidated. Organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs) are known to be involved in metformin uptake and excretion in cells. In this article, we discuss the novel therapeutic possibilities for early-stage endometrial carcinoma (EC) in women with PCOS focusing on metformin, which might have a direct effect in the endometrium through the OCTs and MATEs. We then review the molecular mechanism(s) of the action of metformin in the endometrium and highlight possible mechanistic insights into the inhibition of cell proliferation and tumor growth and, ultimately, the reversal of early-stage EC into normal endometria in women with PCOS.

Murali R, Soslow RA, Weigelt B
Classification of endometrial carcinoma: more than two types.
Lancet Oncol. 2014; 15(7):e268-78 [PubMed] Related Publications
Endometrial cancer is the most common gynaecological malignancy in Europe and North America. Traditional classification of endometrial carcinoma is based either on clinical and endocrine features (eg, types I and II) or on histopathological characteristics (eg, endometrioid, serous, or clear-cell adenocarcinoma). Subtypes defined by the different classification systems correlate to some extent, but there is substantial heterogeneity in biological, pathological, and molecular features within tumour types from both classification systems. In this Review we provide an overview of traditional and newer genomic classifications of endometrial cancer. We discuss how a classification system that incorporates genomic and histopathological features to define biologically and clinically relevant subsets of the disease would be useful. Such integrated classification might facilitate development of treatments tailored to specific disease subgroups and could potentially enable delivery of precision medicine to patients with endometrial cancer.

Related: PTEN

Tomica D, Ramić S, Danolić D, et al.
A correlation between the expression of estrogen receptors and progesterone receptors in cancer cells and in the myometrium and prognostic factors in endometrial cancer.
Coll Antropol. 2014; 38(1):129-34 [PubMed] Related Publications
Endometrial cancer is the most common gynecological malignancy in Croatia. The aim of this study was to determine the immunohistochemical expression of estrogen receptors (ER) and progesterone receptors (PGR) in cancer cells and in the myometrium and to correlate it with prognostic factors of endometrial carcinoma. ER positivity in carcinoma cell nuclei was found in 42 cases (73.7%) and PGR positivity was found in 39 cases (68.4%). Loss of ER in carcinoma cell nuclei correlated with larger tumor size (p = 0.041), poor carcinoma differentiation (p = 0.012), a more aggressive histological type (p < 0.001), lymphovascular space invasion (p = 0.002) and a higher surgical stage (p = 0.037). Loss of PGR in carcinoma cell nuclei correlated with an increased age in patients (p = 0.009), poor tumor differentiation (p = 0.002), a more aggressive histological type (p < 0.001), lymphovascular space invasion (p = 0.002) and a higher surgical stage (p < 0.001). The lower expression of both receptors did not correlate with the depth of myometrial invasion. Regarding the status of receptors in the myometrium, loss of PGR in the myometrium correlated with a more aggressive histological type (p = 0.005) and a lack of ER in the myometrium tended to correlate with tumor growth (p = 0.059). In conclusion, the loss of both hormone receptors in carcinoma cells and loss of PGR in the myometrium was a predictor of a more aggressive type of endometrial cancer and a poor prognosis.

Meng B, Hoang LN, McIntyre JB, et al.
POLE exonuclease domain mutation predicts long progression-free survival in grade 3 endometrioid carcinoma of the endometrium.
Gynecol Oncol. 2014; 134(1):15-9 [PubMed] Related Publications
OBJECTIVE: POLE exonuclease domain mutations were recently found to occur in a subset of endometrial carcinomas and result in defective proof-reading function during DNA replication. The aim of this study is to further characterize the clinical and pathologic significance of POLE exonuclease domain mutations in high-grade endometrial carcinomas.
METHODS: We assessed for mutations in the exonuclease domain of POLE by Sanger sequencing in 53 grade 3 endometrioid, 25 serous, 16 clear cell and 5 dedifferentiated carcinomas. We correlated POLE mutation status with clinicopathologic features and molecular parameters. Univariate and multivariate survival analyses were performed using Kaplan-Meier and cox regression analyses.
RESULTS: POLE exonuclease domain mutations were identified in 8 of 53 (15%) grade 3 endometrioid carcinomas and not in any other histotypes examined. Only 1 of the 8 grade 3 endometrioid carcinomas with POLE exonuclease domain mutation displayed deficient mismatch repair protein expression by immunohistochemistry (MSH6 loss), compared to 21 of 45 grade 3 endometrioid carcinomas with wild-type exonuclease domain. When analyzed together with published grade 3 endometrioid carcinomas by The Cancer Genome Atlas, the presence of POLE exonuclease domain mutation was associated with significantly better progression-free survival in univariate (p=0.025) and multivariate (p=0.010) analyses, such that none of the patients with POLE mutated tumors experienced disease progression
CONCLUSIONS: POLE exonuclease domain mutations occur in a subset of grade 3 endometrioid carcinomas and are associated with good clinical outcome. It can serve as an important prognostic molecular marker to guide the management of patients with grade 3 endometrioid carcinomas.

Albores-Saavedra J, Dorantes-Heredia R, Chablé-Montero F, et al.
Endometrial stromal sarcomas: immunoprofile with emphasis on HMB45 reactivity.
Am J Clin Pathol. 2014; 141(6):850-5 [PubMed] Related Publications
OBJECTIVES: We describe the morphologic and immunohistochemical features of 17 endometrial stromal neoplasms, 16 sarcomas, and one stromal nodule.
METHODS: We reviewed 35 cases interpreted as endometrial stromal neoplasms, but 17 high-grade endometrial stromal sarcomas (ESS) and one case of mixed endometrial sarcoma and leiomyosarcoma were excluded from the study. Data from the Surveillance Epidemiology and End Results program on low- and high-grade ESS for 1973 through 2003 were obtained.
RESULTS: One uterine primary ESS had collections of clear cells (20%), while a metastatic ESS contained predominantly clear cells (90%). CD10 (88.2%) and smooth muscle actin (70.5%) were the most common positive immunohistochemical markers. The latter marker was located in the cytoplasm in 47% of the ESS and in the nucleus in 23.5%, a previously unreported feature. HMB45 was detected in 23.5% of the ESS, which contrasts with the 2% reported by other authors.
CONCLUSIONS: The presence of clear cells and HMB45 reactivity does not justify the term perivascular epithelioid cell tumors for these neoplasms. Two of 17 patients with ESS died of metastatic disease. However, among 274 cases of ESS (all stages included) collected by the Surveillance Epidemiology and End Results Program of the National Cancer Institute during a 30-year period, the 10-year survival rate was 94%.

Wilkinson-Ryan I, Binder PS, Pourabolghasem S, et al.
Concomitant chemotherapy and radiation for the treatment of advanced-stage endometrial cancer.
Gynecol Oncol. 2014; 134(1):24-8 [PubMed] Related Publications
INTRODUCTION: Ccombination chemotherapy and radiation therapy is used for adjuvant treatment of stage III-IV endometrial cancer. The goal of this study was to review the treatment duration, toxicity, and survival for patients treated with concomitant chemotherapy and radiation.
METHODS: Women with stage III-IV endometrial cancer treated with concurrent chemotherapy and radiation between 2006 and 2013 were included. Toxicities were classified per CTCAE v3.0 and RTOG/EORTC late radiation morbidity scoring. Descriptive statistics were used to quantify treatment and toxicities. Kaplan-Meier method was used to estimate survival.
RESULTS: Fifty-one patients met our inclusion criteria. Median age was 60 (range 33-85). Thirty-six patients (70.6%) had endometrioid histology, 13 patients (25.5%) had serous, clear cell, or mixed histology, and 2 women (3.9%) had carcinosarcoma. Forty-eight patients had stage III disease and three patients were stage IVB. Mean treatment duration was 107 ± 19 days. Forty-two patients received all planned chemotherapy, and 16 patients required a dose reduction. Thirty-four patients (66.7%) experienced grade 3-4 toxicities, the majority of which were hematologic. There were no deaths related to therapy. Eighty-six percent of patients received leukocyte growth factors, and 25% of patients received a blood transfusion. Seven late grade 3-4 complications occurred: four gastrointestinal and two genitourinary, and one patient had ongoing neuropathy. Median progression-free survival was 42.8 months (range 4.4-81.5 months) and median overall survival was 44.9 months (range 5.1-82.6 months). Three-year overall survival was 80%.
CONCLUSION: Concomitant chemotherapy and radiation is an adequately tolerated treatment modality that allows for shorter treatment duration.

Related: Carboplatin Ifosfamide Paclitaxel

Ruiz I, Martín-Arruti M, Lopez-Lopez E, Garcia-Orad A
Lack of association between deficient mismatch repair expression and outcome in endometrial carcinomas of the endometrioid type.
Gynecol Oncol. 2014; 134(1):20-3 [PubMed] Related Publications
OBJECTIVE: Endometrial carcinomas of the endometrioid type (EEC) are associated with a good prognosis. However, about 20% of them recur and new prognostic markers are needed. Microsatellite instability (MSI), associated with mismatch repair (MMR) deficiency, is a frequent alteration in EECs that has been associated with prognosis. However, its prognostic impact on EECs remains unclear. The aim of the present study was to clarify the relationship between MMR deficiency and outcome in a large cohort of well classified EECs.
METHODS: A total of 212 EEC samples were analyzed by immunohistochemistry for the MMR genes MLH-1, MSH-2, MSH-6 and PMS-2. Kaplan-Meier survival analysis and log-rank tests were performed to study the prognostic significance of dMMR taking into account clinical and pathological parameters.
RESULTS: We observed no association between MMR deficiency and OS or PFS in our 212 EEC patients (p-value=0.6565 and 0.4380, respectively). When we performed the analysis in different FIGO-stage groups, we did not find association between MMR and OS or PFS in stages I, I/II or III/IV. When we analyzed the specific group of patients with lymphatic invasion separately, MMR expression was not associated with OS or PFS either.
CONCLUSIONS: MMR deficiency does not seem to be a good prognostic marker in endometrioid type endometrial carcinomas.

Related: MSH6 MSH2

Gao C, Wang Y, Tian W, et al.
The therapeutic significance of aromatase inhibitors in endometrial carcinoma.
Gynecol Oncol. 2014; 134(1):190-5 [PubMed] Related Publications
OBJECTIVE: To review recent studies about the application of aromatase inhibitors in endometrial carcinoma and the benefits and challenges of aromatase inhibitors in this regard.
METHODS: Relevant studies and manuscripts were searched for in Pubmed using the following terms, either alone or in combination: aromatase, aromatase inhibitors, letrozole, anastrozole, endometrial cancer, breast cancer, endocrine, therapy, and side effects.
RESULTS: Endometrial carcinoma is one of the most pervasive gynecological malignancies. Type I endometrial carcinoma is estrogen-dependent. Recent studies have demonstrated that aromatase inhibitors, which interfere with estrogen biosynthesis by inhibiting the activity of aromatase, can be used to treat endometrial carcinoma and its precancerous lesions to some extent. In early-stage endometrial carcinoma or atypical hyperplasia, a precancerous lesion of endometrial carcinoma, the effects of aromatase inhibitors were promising. However, in advanced or recurrent endometrial carcinoma, the application of aromatase inhibitors cannot solve the problem evidently. In addition, these inhibitors have limitations, like side effects and drug resistance. The need for a new generation of inhibitors with higher specificity and fewer side effects should be studied further.
CONCLUSIONS: Aromatase inhibitors show promise in the therapy of endometrial carcinoma, especially the early stage. Further studies should be conducted to develop next-generation aromatase inhibitors with higher specificity and fewer side effects.

Bendifallah S, Canlorbe G, Raimond E, et al.
A clue towards improving the European Society of Medical Oncology risk group classification in apparent early stage endometrial cancer? Impact of lymphovascular space invasion.
Br J Cancer. 2014; 110(11):2640-6 [PubMed] Article available free on PMC after 27/05/2015 Related Publications
BACKGROUND: Lymphovascular space invasion (LVSI) is one of the most important predictors of nodal involvement and recurrence in early stage endometrial cancer (EC). Despite its demonstrated prognostic value, LVSI has not been incorporated into the European Society of Medical Oncology (ESMO) classification. The aim of this prospective multicentre database study is to investigate whether it may improve the accuracy of the ESMO classification in predicting the recurrence risk.
METHODS: Data of 496 patients with apparent early-stage EC who received primary surgical treatment between January 2001 and December 2012 were abstracted from prospective multicentre database. A modified ESMO classification including six risk groups was created after inclusion of the LVSI status in the ESMO classification. The primary end point was the recurrence accuracy comparison between the ESMO and the modified ESMO classifications with respect to the area under the receiver operating characteristic curve (AUC).
RESULTS: The recurrence rate in the whole population was 16.1%. The median follow-up and recurrence time were 31 (range: 1-152) and 27 (range: 1-134) months, respectively. Considering the ESMO modified classification, the recurrence rates were 8.2% (8 out of 98), 23.1% (15 out of 65), 25.9% (15 out of 58), and 45.1% (28 out of 62) for intermediate risk/LVSI-, intermediate risk/LVSI+, high risk/LVSI-, and high risk/LVSI+, respectively (P<0.001). In the low risk group, LVSI status was not discriminant as only 7.0% (14 out of 213) had LVSI+. The staging accuracy according to AUC criteria for ESMO and ESMO modified classifications were of 0.71 (95% CI: 0.68-0.74) and 0.74 (95% CI: 0.71-0.77), respectively.
CONCLUSIONS: The current modified classification could be helpful to better define indications for nodal staging and adjuvant therapy, especially for patients with intermediate risk EC.

Cruz-Galarza D, Pérez-Rodríguez O, Laboy-Torres J, Gutiérrez-Rivera S
An unusual case of a borderline Brenner tumor associated with bilateral serous cystadenoma and endometrial carcinoma.
Bol Asoc Med P R. 2014; 106(1):54-6 [PubMed] Related Publications
Brenner tumor accounts for 1.5 to 2.5% of ovarian tumors. Nearly all are benign and 1% malignant. Less than twenty-five cases of borderline Brenner tumor have been reported worldwide. Our case is the first one related to a bilateral ovarian serous cystadenofibroma and endometrioid adenocarcinoma. This unusual case increases the limited data for borderline Brenner tumors.

Related: Breast Cancer Ovarian Cancer

Popovic MD, Banicevic AC, Popovic B, et al.
Treatment of endometrial cancer in patient with malignant obesity.
Med Arch. 2014; 68(1):69-70 [PubMed] Related Publications
Our 60-year-old patient menarche in 13-year, two delivery, last menstruation in 53-year, without uterine bleeding or any kind of symptomatology. The gynecological transvaginal ultrasound examination showed hyperplasio endometrii (20 mm). After curettage, pathological examination was diagnostic polypus carcinomatoides. The patient with HTA and obesity was admitted to and operated on at the Gynecological Department due to endometrial carcinoma (FIGO stage IA1). Because of her giant obesity, BMI - 71.50 kg/m2, weight 219 kg and height 175 cm, surgery by the abdominal approach was very difficult to perform, so vaginal hysterectomy was carried out. The procedure was completed within 127 minutes without any intraoperative complications. Blood loss was less than 100 ml. The patient was discharged on postoperative day 7. The patient was followed up for 6 months after surgery. No complications or recurrence were reported during the 6-month follow up.

Masui K, Yoshida K, Takenaka T, et al.
A novel minimally invasive technique of high-dose rate image-based intracavitary brachytherapy for endometrial cancer using a single fine and soft, flexible applicator.
Anticancer Res. 2014; 34(5):2537-40 [PubMed] Related Publications
AIM: We report on a minimally invasive computed tomography (CT)/magnetic resonance imaging (MRI)-based image-guided intracavitary brachytherapy (ICBT) for an elder patient with endometrial cancer, who was unfit for anesthesia, using a fine and soft flexible applicator.
PATIENTS AND METHODS: The patient was an 82-year-old female. She was identified as having T1bN0M0 (stage IB) tumor, and histological findings revealed grade 2 adenocarcinoma. She was contraindicated for surgery because of advanced age and severe pulmonary emphysema; therefore, she was managed with CT/MRI-based ICBT alone. The total treatment dose was 26 Gy (6.5 Gy per fraction). The dose-volume histogram of the gross tumor volume, the clinical target volume, and organs at risk were calculated.
RESULTS: The patient safely completed the ICBT course without pre-medication. Tumor growth was controlled, with complete disappearance after 32 months. No acute or late adverse effects were observed. MRI-guided ICBT can visualize the gross tumor volume in the uterine body, which cannot be detected by CT.
CONCLUSION: We successfully and safely performed minimally invasive CT/MRI-based ICBT without pre-medication in a patient with endometrial cancer with high surgical risks, using a fine and soft, flexible applicator.

Related: Brachytherapy

Tinelli R, Litta P, Meir Y, et al.
Advantages of laparoscopy versus laparotomy in extremely obese women (BMI>35) with early-stage endometrial cancer: a multicenter study.
Anticancer Res. 2014; 34(5):2497-502 [PubMed] Related Publications
BACKGROUND: The aim of the present study was to demonstrate the advantages of laparoscopy versus laparotomy for treatment of extremely obese women with early-stage endometrial cancer.
MATERIALS AND METHODS: Seventy-five extremely obese patients with Body Mass Index >35 kg/m(2) and clinical stage I endometrial cancer underwent hysterectomy and bilateral salpingo-oophorectomy, and in all cases we performed systematic pelvic lymphadenectomy by laparoscopy (mean BMI of 38±7.3 kg/m(2)) or laparotomy (mean BMI of 39±8.1 kg/m(2)).
RESULTS: In two (4.4%) patients of the laparoscopy group we observed a port site haematoma that was resolved without a second surgery. In three patients of the laparotomy-group, we observed dehiscence of the abdominal suture with surgical site infection that was re-sutured.
CONCLUSION: Laparoscopy can be considered a safe and effective therapeutic procedure for managing early-stage endometrial cancer in extremely obese women with a lower complication rate, lower surgical site infection and postoperative hospitalization.

Nakao Y, Yamasaki F, Yokoyama M, et al.
Minimal deviation endometrioid adenocarcinoma of the endometrium and its MRI findings.
Eur J Gynaecol Oncol. 2014; 35(2):185-7 [PubMed] Related Publications
Minimal deviation endometrioid adenocarcinoma (MDA-E) of the endometrium is a rare pathological entity, and its radiological features are rarely documented. A 73-year-old Japanese woman was referred to the authors when an endometrial biopsy revealed moderately differentiated endometrioid adenocarcinoma. Preoperative radiological examinations, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) showed no evidence of cancer nests. In the hysterectomy specimen, mildly atypical glands were scattered throughout the entire depth of the myometrium, without stromal desmoplastic reaction, and a tiny focus of typical, ruptured, endometrioid adenocarcinoma glands was found in the atrophic endometrium. MRI had not been able to identify this unusual, scattered, myometrial invasion. It should be kept in mind that in cases showing Stage IA endometrial carcinoma without endometrial thickening on MRI, this rare form of invasion may be present.

Toptas T, Tasova-Yildirim G, Karaveli S, Simsek T
Malignant mixed Müllerian tumor with small cell neuroendocrine differentiation: a case report and review of the literature.
Eur J Gynaecol Oncol. 2014; 35(2):180-4 [PubMed] Related Publications
INTRODUCTION: Small cell neuroendocrine differentiation (NE) in malignant mixed Müllerian tumors (MMMTs) is a rare and unusual occurrence with very few previously reported cases. There is no consensus regarding its diagnosis, classification, and optimal treatment options.
CASE: The authors report a patient with endometrial MMMT and NE differentiation who initially received comprehensive surgery followed by adjuvant chemotherapy containing cisplatin and etoposide. She further underwent metastasectomy and received carboplatin and paclitaxel for the relapse. She is still alive 12 months after the diagnosis. The authors performed a review of literature in order to characterize the clinical phenotype. These patients have a very aggressive disease. Median life expectancy seems to be less than a year.
CONCLUSIONS: It is reasonable to perform comprehensive staging surgery followed by adjuvant chemotherapy irrespective to stage of the disease.

Goiri Little C, Ruiz Sautua R, Martínez Gallardo L, et al.
Chylous ascites after retroperitoneal aortocava lymphadenectomy for endometrial cancer: a case report.
Eur J Gynaecol Oncol. 2014; 35(2):178-9 [PubMed] Related Publications
This is a case report of chylous ascites after retroperitoneal aortocava lymphadenectomy for endometrial cancer. There are few reports of chylous ascites in gynecologic surgery. Treatment is primarily conservative. The present case was resolved with a low fat diet with medium-chain triglyceride (MCT) supplements and somatostatin IV.

Wong LF, Wahab NA, Gleeson N
Appendectomy with cytoreductive surgery for ovarian and type 2 endometrial carcinoma.
Eur J Gynaecol Oncol. 2014; 35(2):143-8 [PubMed] Related Publications
UNLABELLED: There is considerable variation within and between cancer centers in the practice of appendectomy as part of cytoreductive surgery for ovarian carcinoma and in the surgical staging of endometrial carcinoma. The purpose of this study was to determine the prevalence and the type of appendiceal pathology, the morbidity associated with appendectomy in gynaecologic cancer surgery.
MATERIALS AND METHODS: This is a retrospective review of all cytoreductive surgery for ovarian carcinoma and surgical staging for endometrial carcinoma with appendectomy over a four year period.
RESULTS: Two hundred and fifty-one patients (38 patients for endometrial carcinoma surgery and 213 patients for ovarian cytoreduction) had an appendectomy performed. Metastases to the appendix was present in 46 (23.2%) of primary ovarian carcinoma and one (2.6%) primary endometrial carcinosarcoma. The appendix was more likely to be involved in advanced stage ovarian cancer with positive peritoneal washings, omental deposits, grade 3 differentiation, and papillary serous histology. Sixteen (6.4%) co-incidental primary appendiceal tumours were detected. No postoperative morbidity specific to appendectomy was identified. One case of ovarian carcinoma was upstaged from IC to IIIA by the appendiceal metastases. There was no upstaging of disease in the endometrial carcinoma group.
DISCUSSION: Appendectomy is an integral part of ovarian cytoreductive surgery but the authors found it did not upstage the disease in a clinically significant manner. The incidence of co-incidental appendiceal primary tumours was high in this series and may add value to the procedure in preventing further surgeries. The absence of procedure related morbidity is reassuring. The authors recommend appendectomy for all ovarian staging surgery and its consideration in type 2 endometrial cancer.

Related: Gastrointestinal Carcinoid Tumours Ovarian Cancer

Taskiran C, Erdem O, Onan A, et al.
Maspin expression in endometrial hyperplasia and carcinoma, and its relation with angiogenesis.
Eur J Gynaecol Oncol. 2014; 35(2):134-9 [PubMed] Related Publications
AIM: The purpose of this study was to evaluate the maspin expression in endometrial hyperplasia and cancer, and also to investigate its relation with angiogenesis.
MATERIALS AND METHODS: A total of 19 women with complex atypical hyperplasia, 44 patients with simple hyperplasia without atypia, and 67 patients with endometrial carcinoma were included. Maspin expression was assessed by immunohistochemistry (IHC), and tested for possible significant relation with age, FIGO stage, histologic type, grade, depth of myometrial invasion (MI), lymphovascular space involvement (LVSI), lymph node metastasis, and overall survival (OS). Angiogenesis was determined by vascular endothelial growth factor (VEGF) staining.
RESULTS: Maspin expression was detected in only three patients with endometrial hyperplasia (5%). In patients with endometrial cancer, cytoplasmic and nuclear maspin expressions were detected in 36 (53.7%) and 18 (26.9%) patients, respectively. No significant relation was noted between staining localizations and prognostic variables. The five-year OS rate for patients with cytoplasmic staining was 91%, compared to 87% for patients without staining (p = 0.31). These values for nuclear expression were 100% and 87%, respectively (p = 0.16). The cytoplasmic and nuclear maspin expressions were found to be significantly correlated with VEGF (r = 0.278, p = 0.02 and r = 0.295, p = 0.01, respectively).
DISCUSSION: This is the first study to demonstrate the relation between maspin expression and angiogenesis in endometrial cancer. Although no survival difference was noted for cytoplasmic or nuclear maspin expressions, a tendency was detected for nuclear staining. Further series will clarify the exact prognostic role of maspin expression in gynecological malignancies including endometrial cancer.

Related: Angiogenesis and Cancer VEGFA SERPINB5

Koh YV, Tang JI, Choo BA, et al.
Adjuvant radiotherapy for endometrial cancer--a comparative review of radiotherapy technique with acute toxicity.
Eur J Gynaecol Oncol. 2014; 35(2):128-33 [PubMed] Related Publications
OBJECTIVES: The addition of pelvic radiotherapy to brachytherapy (EBRT-BT) in early-stage endometrial cancer is controversial and may cause unnecessary toxicity. The incidence of acute toxicity of EBRT-BT will have an impact on clinical decision and patient compliance but is currently poorly understood. This study compares the acute toxicities of EBRT-BT versus BT alone.
MATERIALS AND METHODS: Seventy-nine patients with FIGO Stage IA-II endometrial cancer who underwent adjuvant radiotherapy, (EBRT-BT or BT alone) from 2001 to 2011 were included in the study. Medical records of these patients were reviewed retrospectively and toxicity graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Patients were followed up for at least three months post-treatment to assess resolution of toxicity.
RESULTS: The mean age of the study group was 60.6 years. Median follow-up was four years. Forty patients received EBRT-BT. There was a 37% increase in Grade 1-3 diarrhea with the addition of pelvic radiotherapy (OR 18.67, p < 0.0005) and a 34% increase in lethargy (p < 0.0005). There was also an increased occurrence of genitourinary and skin toxicities. Two patients in the EBRT-BT group required hospitalisation for severe diarrhea and three patients were unable to complete the treatment. All acute toxicities had resolved by three months post treatment.
CONCLUSION: EBRT-BT causes significantly more acute toxicities compared to BT alone. Patients should be informed of this during counselling.

Related: Brachytherapy

Gadducci A, Cosio S, Landoni F, et al.
Adjuvant treatment and analysis of failures in patients with high-risk FIGO Stage Ib-II endometrial cancer: an Italian multicenter retrospective study (CTF study).
Gynecol Oncol. 2014; 134(1):29-35 [PubMed] Related Publications
OBJECTIVES: The purpose of this retrospective study was to assess the clinical outcome of patients with high-risk, early-stage endometrioid endometrial cancer (stage Ib or II with myometrial invasion >50%, grade 2-3).
METHODS: We assessed 192 patients who underwent hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy, had histologically negative pelvic nodes, and had negative CT findings for aortic node involvement.
RESULTS: Tumor relapsed in 36 patients after a median time of 21.2 months. The recurrence was vaginal in 7 (19.4%), distant in 16 (44.4%), aortic in 8 (22.2%), and involved multiple sites in 5 (13.9%). There was a trend to a lower vaginal recurrence rate in the 143 patients who received adjuvant radiotherapy (+chemotherapy) compared with the 46 who did not (2.1% versus 8.7%). Distant or aortic recurrences were lower in the 37 patients who received adjuvant chemotherapy (+radiotherapy) than in the 152 who did not (2.7% versus 18.4%, p=0.02). Of the 29 patients who received sequential adjuvant chemotherapy and radiotherapy, none developed local recurrence and only one had distant recurrence. There was a trend for a better 5-year progression-free survival and overall survival for the patients who received chemotherapy (+radiotherapy) compared with those who did not (86.0% versus 71.3%, and 92.3% versus 75.6%, respectively).
CONCLUSIONS: Our data appear to suggest that adjuvant chemotherapy reduces the risk of distant or aortic recurrences and that sequential adjuvant chemotherapy and radiotherapy achieve an excellent local and distant control of disease in these clinical settings.

Prakansamut N, Sirayapiwat P, Triratanachat S
The percentages of endometrial hyperplasia and endometrial cancer among polycystic ovary syndrome (PCOS) patients presenting with abnormal menstrual pattern.
J Med Assoc Thai. 2014; 97(2):159-64 [PubMed] Related Publications
OBJECTIVE: Assess the occurrence of endometrial hyperplasia and endometrial cancer among PCOS patients having abnormal menstrual pattern. Endometrial thickness and other clinical characteristics associated with endometrial hyperplasia and endometrial cancer were also evaluated
MATERIAL AND METHOD: Women with PCOS and abnormal menstrual pattern were enrolled into this cross-sectional study. Endometrial thicknesses were evaluated using transvaginal sonography. Endometrial aspiration was performed with endometrial aspirator and sent for pathology.
RESULTS: Out of 52 PCOS patients with abnormal menstrual pattern, nine (17.3%) and one (1.9%) had endometrial hyperplasia and endometrial cancer, respectively. There was no significant difference in mean endometrial thickness between those who had abnormal and normal endometrium (8.19 +/- 2.58 mm and 7.76 +/- 4.03 mm, respectively). However BMI and age of patients with abnormal endometrium were significantly higher and older than those with normal endometrium (p = 0.031 and p = 0.009, respectively).
CONCLUSION: Nineteen point two percent (19.2%) of patients with PCOS and abnormal menstrual pattern had endometrial hyperplasia or endometrial cancer Endometrial thickness was not different between those with abnormal and normal endometrium.

Related: Thailand

Mozos A, Catasús L, D'Angelo E, et al.
The FOXO1-miR27 tandem regulates myometrial invasion in endometrioid endometrial adenocarcinoma.
Hum Pathol. 2014; 45(5):942-51 [PubMed] Related Publications
Micro-RNA (miRNA) signatures influence the prognosis of cancer, but little is known about their role in myometrial invasion in endometrioid endometrial adenocarcinoma (EEC). We studied miRNA expression signatures in noninvasive and invasive EEC focusing on the alteration of miR-27 and its main target, FOXO1 as well as their relationship with the clinicopathological parameters and other genetic alterations such as PIK3CA mutations. In 25 tumors and 5 normal endometria, unsupervised hierarchical clustering analysis showed that normal endometria and noninvasive EEC were grouped together and separately from invasive and advanced stage tumors. Of the 20 miRNAs differentially expressed in noninvasive (stage IA) and myoinvasive adenocarcinomas (stage IB and IC), miR27 was overexpressed in invasive adenocarcinomas, and its expression increased linearly according to stage. Results were validated by quantitative real-time reverse transcription polymerase chain reaction in an independent series of 44 EEC. By in situ hybridization, miR-27 expression was limited to the stroma. Using quantitative real-time reverse transcription polymerase chain reaction, the expression of proapoptotic transcription factor FOXO1 was down-regulated in invasive compared with noninvasive tumors. Furthermore, we found that the expression of active caspase 3 was higher in noninvasive than invasive EEC. When stratified by PIK3CA mutations, all invasive tumors down-regulated FOXO1, but only nonmutated adenocarcinomas showed miR-27 overexpression. In conclusion, we propose that the miR27-FOXO1 tandem inhibits apoptosis and represents an alternative pathway for tumor cell survival in PIK3CA-nonmutated EEC.

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