Stage Endometrial Carcinoma Research Articles

Abstract 1525: Nuclear homeoprotein SIX1 is associated with stage and grade of endometrial carcinoma.

Abstract Introduction: SIX1 is a member of the homeoprotein gene family encoding transcription factors involved in normal embryogenesis. These proteins function in the cell nucleus to regulate transcription of genes that drive differentiation. SIX1 is also aberrantly expressed in numerous human malignancies, including breast, ovarian and cervical carcinomas. In a mouse model, SIX1 initiates transformation of mammary epithelial cells to diverse histologic types of carcinoma. SIX1 has not yet been studied in endometrial carcinoma, which is the most common gynecologic malignancy in the United States. Thus, our goal was to evaluate SIX1 in clinical samples of endometrial carcinoma and determine if there was an association with stage and grade. Methods: A tissue microarray (TMA) was created using endometrial carcinoma cases (n=55) and benign controls (i.e. proliferative, secretory and atrophic endometrium) (n=12). Endometrioid and serous histologic types were included in the carcinoma cases. The TMA was stained using a rabbit polyclonal anti-SIX1 antibody (Sigma). The TMA was then scored in a blinded manner by a single pathologist, using presence versus absence of nuclear staining for the stromal cells and the epithelial cells. Clinical data was collected on these samples to include height, weight, BMI, grade (FIGO 1, 2 or 3) and stage (1A, 1B-2B, 3A-4B). Results: Few controls had nuclear SIX1 in epithelial cells while all controls had nuclear SIX1 in stromal cells. In endometrial cancer samples, there was significantly increased nuclear SIX1 staining in the epithelial cells compared to controls, while there was less nuclear SIX1 in stromal cells. This finding was more pronounced with increasing grade and stage of tumor (Table 1). Conclusions: Nuclear SIX1 expression is associated with increased grade and stage of endometrial cancer. These findings suggest that SIX1 may play a role in the progression of this common cancer and have utility as a marker of more aggressive disease. Table 1. Percentage of uterine samples with nuclear SIX1 staining in epithelial and stromal cells Grade Stage Epithelial Stromal Epithelial Stromal Control 3/12 (25) 12/12 (100) Control 3/12 (25) 12/12 (100) Grade 1 16/22 (72) 13/22 (59) 1A 5/11 (46) 10/11 (91) Grade 2 15/16 (94) 6/16 (38) 1B-2B 26/31 (84) 13/31 (42) Grade 3 14/17 (82) 7/17 (41) 3A-4B 12/13 (92) 3/13 (23) Citation Format: Sara E. Wobker, Wendy N. Jefferson, Carmen J. Williams, Victoria L. Bae-Jump. Nuclear homeoprotein SIX1 is associated with stage and grade of endometrial carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1525. doi:10.1158/1538-7445.AM2013-1525

Impact of Body Mass Index on Tumor Recurrence and Survival for Patients with Early Stage Endometrial Carcinoma after Adjuvant HDR Vaginal Cuff Brachytherapy

Increasing body mass index (BMI) is associated with increased prevalence of endometrial carcinoma (EC). We sought to investigate the significance of BMI as a prognostic factor for tumor recurrence and survival in women with early stage endometrial carcinoma who were treated with adjuvant HDR vaginal cuff brachytherapy. In our prospectively-maintained database of patients with endometrial cancer, we identified 141 patients who underwent surgical staging between 1990 and 2010 for FIGO stage I-II and received adjuvant high-dose-rate vaginal cuff brachytherapy. Their medical records were retrospectively reviewed in this IRB-approved study. Height and weight data were available at time of hysterectomy from which BMI was calculated (<30, ≥30 - <38 and ≥38). Following a univariate analysis, multivariable modeling was done using Cox regression analysis. Median followup was 48 months (range 13-245), median age was 62 years (range 39-91) and median BMI is 33.7 (range 19.7 - 63.6). There were 126 patients (89.4%) with endometrioid histology, 96 patients (68%) with stage IA, 38 patients 27% with stage IB and 7 (5%) with stage II. Median brachytherapy dose was 37.5 Gy to the surface of a vaginal cylinder in 5 fractions. Only 13 patients (9.2%) received adjuvant chemotherapy. There were only 6 patients with recurrences including only one patient with isolated vaginal cuff recurrence. Due to small number of events and based on exploratory analysis, body mass index (as a continuous variable or categorical) was not a significant predictor of recurrence-free, or disease-specific survival. BMI ≥38 and older age were the only independent predictor of OS (p=0.02 and <0.001, respectively). Five-year recurrence-free, disease-specific and overall survival for the study cohort was 93.2%, 96.3% and 89%, respectively. In our study, vaginal cuff control was excellent with vaginal brachytherapy. Body mass index was not a predictor of tumor recurrence or disease-specific survival in patients with early stage endometrial carcinoma who underwent surgical staging followed by adjuvant vaginal cuff HDR brachytherapy.

Long-Term Clinical Outcome of Women with Stage I-II Endometrial Adenocarcinoma after Adjuvant Intravaginal High-Dose-Rate Brachytherapy Alone

Vaginal cuff brachytherapy is proven to be an effective and well tolerated adjuvant radiation treatment modality after hysterectomy in women with early stage endometrial carcinoma. However, there remains paucity of data in regards to long-term clinical outcome endpoints. In this IRB-approved retrospective study, 141 women with 2009 FIGO stage I-II endometrial adenocarcinoma were identified. All patients underwent hysterectomy followed by adjuvant intravaginal HDR brachytherapy. Various prognostic factors were analyzed using Cox proportional hazards regression. All patients underwent hysterectomy between 1990 and 2010 with at least one year followup after hysterectomy. Median followup was 48 months (range 13-245). Median age at diagnosis for the study cohort was 62 years (range of 39 to 91). Ninety-six patients (68.1%), 38 patients (27%), and 7 patients (5%) had stages IA, IB, and II endometrial adenocarcinoma, respectively. One hundred twenty-six patients (89.4%) had endometrioid carcinoma. The median number of lymph nodes sampled was 10 (range of 5-68). Peritoneal cytology was negative for malignant cells in all patients. All patients received adjuvant high-dose-rate vaginal brachytherapy through single channel vaginal cylinder. Median brachytherapy surface dose was 37.5 Gy in 5 fractions to the upper 3-4 cm of the vagina. Thirteen patients (9.2%) had adjuvant platinum-based chemotherapy. None of the patients reported more than grade 1 vaginal toxicity according to common toxicities criteria version 3.0. Only 6 patients (4.3%) were diagnosed with tumor recurrence including only one patient with an isolated vaginal recurrence. Five-year relapse-free, disease-specific, and overall survival rates were 93.2%, 96.3% and 89%, respectively. Due to small number of recurrences and based on exploratory analysis, there were no significant predictors of relapse-free or disease-specific survival. As expected, age as a continuous variable was the only variable that was a significant predictor of overall survival (p<0.001). Our results suggest that vaginal cuff brachytherapy alone provides excellent long-term control in patients with early stage endometrial carcinoma after surgical staging. The treatment is very well tolerated with minimal patient-reported side effects.

Optimal Active Length of Vaginal Cuff High-Dose-Rate Brachytherapy in the Adjuvant Treatment of Endometrial Cancer: A University of Louisville Experience

and received adjuvant high-dose-rate vaginal cuff brachytherapy. Their medical records were retrospectively reviewed in this IRB-approved study. Height and weight data were available at time of hysterectomy from which BMI was calculated (!30, $30 -!38 and $38). Following a univariate analysis, multivariable modeling was done using Cox regression analysis. Results: Median followup was 48 months (range 13-245), median age was 62 years (range 39-91) and median BMI is 33.7 (range 19.7 63.6). There were 126 patients (89.4%) with endometrioid histology, 96 patients (68%) with stage IA, 38 patients 27% with stage IB and 7 (5%) with stage II. Median brachytherapy dose was 37.5 Gy to the surface of a vaginal cylinder in 5 fractions. Only 13 patients (9.2%) received adjuvant chemotherapy. There were only 6 patients with recurrences including only one patient with isolated vaginal cuff recurrence. Due to small number of events and based on exploratory analysis, body mass index (as a continuous variable or categorical) was not a significant predictor of recurrence-free, or disease-specific survival. BMI $38 and older age were the only independent predictor of OS (p50.02 and!0.001, respectively). Five-year recurrence-free, disease-specific and overall survival for the study cohort was 93.2%, 96.3% and 89%, respectively. Conclusions: In our study, vaginal cuff control was excellent with vaginal brachytherapy. Body mass index was not a predictor of tumor recurrence or disease-specific survival in patients with early stage endometrial carcinoma who underwent surgical staging followed by adjuvant vaginal cuff HDR brachytherapy.

Squamous Cell Carcinoma of the Vaginal Vault Following Whole Pelvic Radiation Therapy and Surgery

Abstract Background: Here, we report the case of a patient with endometrial carcinoma stage IB who was diagnosed with squamous cell carcinoma of the vaginal vault 10 years after radiotherapy. Case: A 55-year-old female patient with endometrial carcinoma FIGO stage IB received pelvic irradiation and underwent surgery for her disease. After 10 years, she experienced vaginal bleeding and was subsequently diagnosed with squamous cell carcinoma of the vaginal vault. No distant metastases were identified and the patient was not a candidate for surgery. She received chemotherapy using a combination of 5-fluoruracil and cisplatin, but it was ineffective. The patient is still alive with a progressive disease. Conclusion: Long-term follow-up and aggressive investigation, which even include tissue biopsy, are mandatory whenever patients with a past medical history of pelvic irradiation experience any pelvic symptoms in order to detect early occult second malignancies. (J GYNECOL SURG 29:56)

Prediction of lymph node and distant metastasis in patients with endometrial carcinoma: A new model based on demographics, biochemical factors, and tumor histology

ObjectiveTo develop a model that might predict the probability of lymph node and distant metastasis (stages IIIC–IV) in endometrial carcinoma. MethodsWe studied 774 patients with endometrial carcinoma treated in a single institution. Demographic factors, biochemical factors and preoperative tumor characteristics, identified as potential risk factors for advanced carcinoma in unadjusted analyses, were used to create a logistic regression model with lymph node and distant metastasis as the dependent variable. Statistically significant odds ratios in the regression model were rounded to the nearest whole number. These rounded values were the estimated weights for each factor that were summed to generate a score that might predict the probability of stage IIIC–IV carcinoma. ResultsBiochemical factors and preoperative tumor characteristics predicted lymph node and distant metastasis in the regression model, whereas demographic factors were without effect. The score combining weighted risk factors was: (2×leukocytosis)+(3×thrombocytosis)+(7×elevated CA125)+(4×high-risk histology). The area under curve (AUC) for this total score was 0.823, with 71.6% sensitivity, 75.2% specificity, 25.9% positive predictive value, and 95.7% negative predictive value, using 6 as cut-point. After excluding stage IV carcinomas from the dataset, the AUC was 0.813 for the total score in predicting nodal involvement (P=0.82 vs. total score in predicting stage IIIC–IV carcinomas in the complete dataset). ConclusionsBased on the high negative predictive value, this prediction model could be applied for identifying patients who may not benefit from lymphadenectomy for endometrial carcinoma staging.

Abdominopelvic washings: A comprehensive review.

Intraperitoneal spread may occur with gynecological epithelial neoplasms, as well as with non-gynecological malignancies, which may result in serosal involvement with or without concomitant effusion. Therefore, washings in patients with abdominopelvic tumors represent important specimens for cytologic examination. They are primarily utilized for staging ovarian cancers, although their role has decreased in staging of endometrial and cervical carcinoma. Abdominopelvic washings can be positive in a variety of pathologic conditions, including benign conditions, borderline neoplastic tumors, locally invasive tumors, or distant metastases. In a subset of cases, washings can be diagnostically challenging due to the presence of co-existing benign cells (e.g., mesothelial hyperplasia, endosalpingiosis, or endometriosis), lesions in which there is only minimal atypia (e.g., serous borderline tumors) or scant atypical cells, and the rarity of specific tumor types (e.g., mesothelioma). Ancillary studies including immunocytochemistry and fluorescence in situ hybridization may be required in difficult cases to resolve the diagnosis. This article provides a comprehensive and contemporary review of abdominopelvic washings in the evaluation of gynecologic and non-gynecologic tumors, including primary peritoneal and mesothelial entities.

Surgical Staging of Early Stage Endometrial Cancer: Comparison Between Laparotomy and Laparoscopy.

BackgroundThe aim of the present study was to compare the laparotomy (LT) and laparoscopy (LS) in patients who undergone surgical staging for early stage endometrium cancer.MethodsRetrospective data were collected and analyzed for amount of intraoperative bleeding, complication rates, total resected and laterality specific number of lymph nodes and duration of operation in patients operated with either LT or LS.ResultsSeventy-nine stage I endometrium cancer patients were found to be eligible for the trial purposes: 58 (73.4%) treated by LT and 21 (26.6%) treated by LS. The number of lymph nodes was similar in LT (8.9 ± 5.3) and LS (9.2 ± 4.8) (P = 0.8). In LT group, there was no difference in the number of lymph nodes between the right and left sides (10 ± 5.8 and 8.7 ± 4.8 respectively, P = 0.19); in LS group, the number of lymph nodes resected from the right side was higher than the left side (9.8 ± 5 and 7 ± 3.5 respectively, P = 0.039). The amount of intraoperative bleeding and hospitalization period were significantly higher in LT group. Seventy-nine patients had a median follow-up of 30 months. The two groups were similar for disease-free survival (P = 0.46, log rank test).ConclusionsThere was no significant difference between the two methods in terms of number of total resected lymph nodes. In early stage endometrial carcinoma, LS has provided adequate staging and similar survival rates with LT.

Recurrence-free and 5-year survival following robotic-assisted surgical staging for endometrial carcinoma

ObjectiveThe aim of this study is to report recurrence-free and overall survival for women with endometrial adenocarcinoma who were surgically staged using robotic-assisted laparoscopy. MethodsA retrospective chart review was performed for all consecutive endometrial adenocarcinoma patients surgically staged with robotic-assisted laparoscopy at the University of North Carolina Hospital from 2005 to 2010. Demographic data, 5-year survival, and recurrence-free intervals were analyzed. Statistical analysis using Chi-square, t-test, and Kaplan–Meier curves were performed with SAS software. Study results were compared to endometrial cancer statistics from the Surveillance Epidemiology and End Results database from the National Cancer Institute. ResultsA total of 499 patients were identified and included in the study. Recurrence-free intervals after robotic-assisted surgical staging were 85.2% for stage IA, 80.2% for stage IB, 69.8% for stage II, and 69% for stage III. Projected 5-year survival was 88.7% for all patients included in the study. Nearly 82% of cases were endometrioid adenocarcinoma, with papillary serous, clear cell or mixed histology comprising 17.4% of cases. Median follow up time was 23months, with a range of 0 to 80months. Among stage IA, IB, II, and III patients, projected overall survival was 94.2%, 85.9%, 77.4%, and 68.6%, respectively. ConclusionsThe results from this study demonstrate that robotic-assisted surgical staging for endometrial cancer does not adversely affect rates of recurrence or survival. These findings provide further evidence that robotic-assisted laparoscopic surgical staging is not associated with inferior results when compared to laparotomy or traditional laparoscopy.

Problematic issues in the staging of endometrial, cervical and vulval carcinomas

The International Federation of Gynecology and Obstetrics (FIGO) staging of tumours of the uterine corpus, cervix and vulva was revised in 2009. The greatest impact of the revised staging was on carcinomas of the uterine corpus. Uterine sarcomas are now staged separately. Changes to the staging system for vulvar carcinomas largely reflect the significance of lymph node status. Only minor amendments have been introduced for cervical carcinomas, which remain the only gynaecological tumours to be staged clinically. These revisions, based on recent evidence, require careful, more detailed assessment of several histological parameters at each anatomical site. The present review deals with the evidence and rationale underpinning the revisions, and includes practical guidance on tumour staging. This covers the assessment and measurement of myoinvasion and evaluation of cervical, parametrial, serosal and vaginal involvement in carcinomas of the uterine corpus; the identification and accurate measurement of stromal invasion in cervical and vulvar carcinomas; the assessment of unusual variants of carcinoma at each of these sites; and the assessment of lymph node involvement.

Does the type of surgery for early-stage endometrial cancer affect the rate of reported lymphovascular space invasion in final pathology specimens?

Laparoscopically assisted vaginal hysterectomy (LAVH), which usually involves the use of an intrauterine manipulator for optimal surgical control, has been shown to be as effective and safe as conventional total abdominal hysterectomy (TAH) for the staging of endometrial carcinoma. The purpose of this study was to determine whether the use of an intrauterine manipulator was associated with an increase in the pathologic reporting of lymphovascular space invasion (LVSI), which is an important determinant in choosing adjuvant therapy. We hypothesized that intracavitary manipulation and an increase of the intrauterine pressure could cause pseudolymphovascular invasion. We performed a retrospective chart review of endometrial cancer patients treated at our institution from January 1996 through January 2006. Records were reviewed for patient's age, preoperative diagnosis, procedure type, final surgical staging, and final pathology report. Using the 2009 International Federation of Gynecology and Obstetrics staging, we included all patients having stage IA or IB endometrioid-type endometrial cancer who had undergone either a TAH or LAVH with or without pelvic and paraaortic lymph node dissection. The χ2 and Fisher exact tests were used to measure the association between risk of positive lymphovascular invasion and surgical groups. Of 568 women identified as having endometrioid-type endometrial cancer, 486 (85.6%) met criteria for stage IA-IB endometrioid histology, grade 1, 2, or 3. LVSI was reported in 553/568 cases, with LVSI positivity in 16.9% (n = 96/568). The mean ages of the LAVH and TAH groups were significantly different (59.4 vs 62.4 years, respectively, P = .0050). Also, mean estimated blood loss and uterine weight significantly varied between TAH and LAVH groups (P = .0001 and .008, respectively). For stage IA, 17/220 (7.7%) who had been treated with LAVH had positive LVSI compared with 20/199 (10.1%) of patients receiving TAH (P = .73). For stage IB, 11/25 (44.0%) of patients treated with LAVH had positive LVSI compared with 10/31 (32.3%) of patients receiving TAH (P = .53). The stage I cancer patients were further subdivided into histological grades 1, 2, and 3, and LVSI was not significantly different between TAH and LAVH groups per grade of cancer. We found no differences between TAH and LAVH in early-stage endometrial cancer (stage IA and IB), with respect to the presence of positive peritoneal washings. In early-stage endometrial cancer (stage IA and IB), there were no differences between TAH and LAVH in the final pathologic report of LVSI. The use of an intrauterine manipulator for LAVH was not associated with an increased detection of LVSI.

O521 SURVIVAL AFTER POSTOPERATIVE RADIOTHERAPY FOR EARLY STAGE ENDOMETRIAL CARCINOMA: THE OSLO STUDY REVISITED AFTER UP TO 43 YEARS OF FOLLOW-UP

International Journal of Gynecology & ObstetricsVolume 119, Issue S3 p. S444-S445 Free communication (oral) presentations O521 SURVIVAL AFTER POSTOPERATIVE RADIOTHERAPY FOR EARLY STAGE ENDOMETRIAL CARCINOMA: THE OSLO STUDY REVISITED AFTER UP TO 43 YEARS OF FOLLOW-UP M. Onsrud, M. OnsrudSearch for more papers by this authorK. Lindemann, K. LindemannSearch for more papers by this authorG.B. Kristensen, G.B. KristensenSearch for more papers by this authorC. Tropé, C. TropéSearch for more papers by this author M. Onsrud, M. OnsrudSearch for more papers by this authorK. Lindemann, K. LindemannSearch for more papers by this authorG.B. Kristensen, G.B. KristensenSearch for more papers by this authorC. Tropé, C. TropéSearch for more papers by this author First published: 22 October 2012 https://doi.org/10.1016/S0020-7292(12)60951-5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume119, IssueS3Abstracts of XX FIGO World Congress of Gynecology and ObstetricsOctober 2012Pages S444-S445 RelatedInformation

Comparison of laparoscopy and laparotomy in surgical staging of clinical early stage endometrial cancer: A report of early experiences from Turkey

The objective of this study was to assess the feasibility of laparoscopy (LS) in endometrial carcinoma staging. Clinical early stage endometrial cancer patients (n = 153) staged by LS or laparotomy (LT) were compared. A total of 40 (26.1%) patients were treated by LS and 113 (73.9%) by LT. All patients underwent pelvic lymphadenectomy. Lymphadenectomy has been extended to para-aortic space in 55% of the LS group and 70% of the LT group. The majority of patients had stage I–II disease. The median numbers of removed pelvic and para- aortic lymph nodes were similar in two groups (p values 0.213 and 0.199, respectively). Body mass index (BMI) (kg/m2) was higher in the LT group (31.2 vs 27.4, p < 0.05). Operation time, age, tumour histology, para-aortic lymphadenectomy and complication rates were similar in the two groups. Four (10%) patients in the LS group and 12 (10.6%) in the LT group had recurrence of disease (p = 1.0). There was no statistical difference for overall survival between the two groups. In conclusion, these findings showed that in endometrial carcinoma cases, laparoscopy has provided adequate staging and similar survival rates with laparotomy.

Endometrial carcinoma: MR staging and causes of error

This study was undertaken to prospectively determine the diagnostic capabilities of magnetic resonance (MR) imaging in detecting myometrial and cervical invasion and lymph node involvement in endometrial carcinoma and to identify the causes of errors in staging endometrial carcinoma. Twenty consecutive patients with a histological diagnosis of endometrial carcinoma underwent preoperative MR imaging. MR findings were compared with surgical staging, considered as the standard of reference. In assessing myometrial invasion, MR imaging showed 70% accuracy, 80% sensitivity, 40% specificity, 80% positive predictive value (PPV), and 40% negative predictive value (NPV). In detecting cervical invasion, MR imaging had 95% accuracy, 100% sensitivity, 94.4% specificity, 66.7% PPV, and 100% NPV. In evaluating lymph node involvement, MR imaging showed 100% accuracy, sensitivity, specificity, PPV and NPV. Errors in evaluating myometrial invasion were caused by polypoid tumour, adenomyosis and leiomyomas, whereas those in evaluating cervical invasion were caused by dilatation and curettage. MR imaging is a reliable technique for preoperative evaluation of endometrial carcinoma. Its main limitation is differentiating between stage IA and IB carcinomas, which is not highly important for surgical planning. Cooperation between the gynaecologist and radiologist is mandatory to avoid staging errors.

Endometrial Cancer: Comparison of Patients with Synchronous Primary Carcinoma of the Endometrium and Ovary vs. Endometrial Carcinoma with Ovarian Metastases.

Purpose: The aim of our study was to investigate the rate of secondary carcinomas in patients with endometrial carcinoma (EC). In particular, we wanted to describe the subset of patients with endometrial and simultaneous ovarian carcinoma (OC), including outcomes. The study also compared patients with EC and ovarian metastasis with patients with EC and simultaneous OC. Patients and Methods: Data from 251 patients with primary endometrial carcinoma who underwent surgery in the years 2005-2009 at the Department of Obstetrics and Gynaecology, University of Tübingen, were analysed retrospectively. Results: A total of 28 patients (11.1 %) had a secondary carcinoma: 18 patients (7.1 %) had OC; 9 (3.5 %) patients had a history of breast cancer, and one patient (0.4 %) respectively had simultaneous carcinoma of the vulva or bladder. 14 patients (5.5 %) had advanced stage EC with ovarian metastasis or, in one case, metastasis to the ovarian tube. Patients with ovarian metastasis had a mean age of 71.2 ± 9.2 years at primary diagnosis, making them significantly older compared to patients with EC and simultaneous OC (55.3 ± 11.8 years, p < 0.001). Moreover, patients with ovarian metastasis significantly more often had EC with a higher tumour grade (grade 1: 0, grade 2: 21.4 %, grade 3: 78.6 %) compared to patients with simultaneous EC and OC (grade 1: 11.1 %, grade 2: 77.8 %, grade 3: 11.1 %; p < 0.001). Conclusion: Almost one in 10 patients with EC had a secondary carcinoma. The most common secondary carcinoma was OC followed by breast cancer. This should be taken into account in the diagnosis and therapy of patients with EC. Patients with simultaneous EC and OC were significantly younger than patients with EC and ovarian metastasis. In addition, their tumour had better prognostic features: thus, the tumour grade of the EC was significantly lower. Overall, the prognosis for patients with synchronous EC and OC is better than that for patients with EC and ovarian metastasis.

Is time to recurrence after hysterectomy predictive of survival in patients with early stage endometrial carcinoma?

Purpose/objective(s)To determine the prognostic significance of time to recurrence (TTR) on overall survival (OS) and disease-specific survival (DSS) following recurrence in patients with stage I–II uterine endometrioid carcinoma. Materials/methodsAfter IRB approval, we retrospectively identified 57 patients with recurrent endometrioid carcinoma who were initially treated for FIGO 1988 stages I–II between 1987 and 2009. The Kaplan–Meier approach and Cox regression analysis were used to estimate OS and DSS following recurrence and identify factors impacting outcomes. ResultsMedian follow-up times were 54.8months from hysterectomy and 19.8months after recurrence. Median time to recurrence was 20.2months. Twenty-eight (47%) patients had a recurrence <18months after hysterectomy and 29 (53%) had a recurrence ≥18months. Both groups were evenly matched regarding initial pathological features and adjuvant treatments. The median OS and DSS in patients with TTR<18months was shorter than those with TTR≥18months, but not statistically significant (p=0.216). TTR did not impact outcomes after loco-regional recurrence, but for extrapelvic recurrence, a shorter TTR resulted in worse OS and DSS (p=0.03). On multivariate analysis, isolated loco-regional recurrence (HR 0.28, p=0.001) and salvage radiation therapy (HR 0.47, p=0.045) were statistically significant independent predictors of longer OS following recurrence. TTR as a continuous variable or dichotomized was not predictive of OS or DSS. ConclusionsIn our study, the prognostic impact of time to recurrence was less important than the site of recurrence. While not prognostic for the entire cohort or for patients with loco-regional recurrence, TTR<18months was associated with shorter OS and DSS after extrapelvic recurrence.

Prognostic role of indoleamine 2,3-dioxygenase in endometrial carcinoma

ObjectiveIndoleamine-2,3-dioxygenase (IDO) suppresses the function of T-lymphocytes and is an important immune escape mechanism for cancer. Therefore, it is to be expected that IDO influences prognosis of cancer patients. This study aimed to investigate the prognostic role of IDO expression in a large cohort of endometrial carcinoma (EC) patients. MethodsA tissue microarray containing primary EC tissue of 355 patients treated in a single institution was used to evaluate IDO expression. Expression of IDO was associated with clinicopathological characteristics, survival and previously determined numbers of CD8+ and Foxp3+ T-lymphocytes. ResultsIDOhigh expression was associated with lower numbers of intratumoral CD8+ T-lymphocytes (p=0.031). Next to well-known prognostic parameters, IDOhigh expression was independently associated with poor disease specific survival in the general cohort of EC patients (HR 2.62, 95% C.I. 1.48–4.66, p=0.001) and among patients with early stage EC (HR 3.06, 95% C.I. 1.10–8.54, p=0.032). ConclusionOur results show that IDO expression is associated with poor survival. This provides evidence that further research into the use of IDO blocking agents in cancer treatment is valid where it might be a promising new therapeutic strategy.

Survival after radiation therapy for early-stage endometrial carcinoma: The Oslo study revisited after up to 43 years of follow-up.

5008 Background: There is an ongoing debate regarding the benefit of radiation in patients with early stage endometrial carcinoma. Data on long time risk conferred by radiation is scarce. This study is a long-term follow-up on survival and secondary cancers of a previously published randomized study (Aalders J. et al., Obstet Gynecol 1980; 56: 419-27). Methods: Between 1968 and 1974, 568 patients with endometrial cancer FIGO stage I primarily treated with abdominal hysterectomy and bilateral salpingo-oophorectomy were included in the study. Patients were postoperatively randomized to receive either vaginal radium brachytherapy followed by external pelvic radiation 40 Gy (N=288) or brachytherapy alone (N=280). Survival data and data on incident secondary cancers were obtained by individual linkage to the Registry of Statistics Norway and Cancer Registry of Norway. By the end of follow-up at 1 November 2011, 45 (7.9%) patients were still alive. We used Cox proportional hazards model to estimate hazard ratios (HR) with 95% confidence intervals (95% CI). We also conducted analyses stratified by age groups. Results: After median 21 (range 0-43.4) years of follow-up there was no significant difference in overall survival or relapse free survival between treatment arms with HR of 1.12 (95% CI: 0.95-1.33) and HR 0.88 (95% CI: 0.55-1.40), respectively. Patients treated with external radiation had significantly lower risk of developing locoregional relapse (p&lt;0.001). However, women younger than 60 years had a significant poorer survival after external radiation (HR 1.36; 95% Cl: 1.06-1.76). In this patient group the risk of secondary cancer was significantly increased (HR 1.9; 95% CI: 1.23-3.03). Conclusions: We observed no survival benefit of external pelvic radiation in early stage endometrial carcinoma. In women younger than 60 years, pelvic radiation decreased survival, probably due to increased risk of subsequent second neoplasms. Adjuvant external radiotherapy cannot be recommended to this patient group. Those who have received such treatment might eventually benefit from prolonged post treatment surveillance with respect to secondary cancer.

HMLH1 promoter hypermethylation and MSI status in human endometrial carcinomas with and without metastases

We investigated the methylation status of mismatch repair gene hMLH1 in 80 primary human endometrial carcinomas (ECs) and in 30 metastatic lesions. It was correlated to the expression of hMLH1 protein, microsatellite instability (MSI) of ECs and to the well-known clinico-pathological variables of cancer. The hMLH1 promoter methylation was detected in 24 out of 64 (37.5%) primary ECs but only in one out of 18 (5.6%) metastatic lesions investigated. Promoter hMLH1 hypermethylation was found more often in early stage ECs and was associated with a decrease of hMLH1 protein expression immunohistochemically. An inverse relationship between hMLH1 expression and clinical stage of the disease was found (p=0.048). Interestingly, there was a significant correlation between MSI and hMLH1 protein expression level (p=0.042). MSI phenotype was found more often in EC metastases compared to the primary tumors (66.7% vs 29.3%; p=0.039). However, neither hMLH1 promoter hypermethylation nor MSI was independent predictive factors for patient's outcome. Using an in vitro model we showed that hMLH1 methylation is reversible. These data showed that hMLH1 methylation with a consequent protein decrease occurred early during EC tumorigenesis and may cause a MSI phenotype, which occurs relatively late. MSI may be an important mechanism supporting further the tumor progression. These findings may have importance for the specific chemosensitization of the primary tumors/metastases and can improve our understanding of endometrial carcinogenesis in humans.

Standard 1.5-T MRI of endometrial carcinomas: modest agreement between radiologists

To evaluate pelvic magnetic resonance imaging (MRI) interobserver agreement for the detection of deep myometrial invasion, cervical stroma invasion and lymph node metastases in endometrial carcinoma patients in relation to surgical staging. Fifty-seven patients with histologically confirmed endometrial carcinoma were prospectively included in a study of preoperative 1.5-T MRI. Four radiologists, blinded to patient data, independently reviewed the images for the presence of deep myometrial invasion, cervical stroma invasion and lymph node metastases. Kappa coefficients for interobserver agreement and diagnostic performances for each observer were calculated using final surgical staging results (FIGO 09) as reference standard. Overall agreement among all observers was moderate for cervical stroma invasion (κ = 0.50 [95% CI 0.27-0.73]) and lymph node metastases (κ = 0.56 [0.09-0.80]) and fair for deep myometrial invasion (κ = 0.39 [0.26-0.55]). Sensitivity (specificity) values for the four observers were 72-92% (44-63%) for deep myometrial invasion, 38-63% (82-94%) for cervical stroma invasion and 25-38% (90-100%) for lymph node metastases. Conventional MRI showed only modest interobserver agreement and diagnostic accuracy for detection of deep myometrial invasion, cervical stroma invasion and lymph node metastases. Improved methods are needed for preoperative imaging in the staging of endometrial carcinomas. MRI is an important tool for preoperative endometrial cancer staging. • Staging agreement based on pelvic MRI was modest among different observers. • Preoperative MRI alone was suboptimal in identifying high-risk patients. • Improved imaging and biomarkers may refine preoperative risk stratification in endometrial cancer.