FIGO Grade Research Articles

151 - Assessing the Risk of Pelvic and Para-Aortic Nodal Involvement in Apparent Early-Stage Ovarian Cancer Undergoing Retroperitoneal Staging

Study Objective: To estimate the prevalence of nodal involvement according to various disease characteristics in order to assess the prognostic advantages to have nodal dissection in apparent early-stage epithelial ovarian cancer (eEOC). Design: Retrospective study. Setting: Gynecologic oncology referral center. Patients: Data of consecutive patients undergoing comprehensive staging for eEOC were retrospectively evaluated. Logistic regression and a nomogram-based analysis were used to assess the risk of nodal involvement. Intervention: Retroperitoneal staging including pelvic and para-aortic node dissection. Measurements and Main Results: Overall, 377 patients were included. All patients had nodal dissection including pelvic and para-aortic lymphadenectomy in 366 and 370 cases, respectively. Forty-four (11.7%) patients were upstaged due to nodal involvement. Pelvic and para-aortic nodal metastases were observed in 32/366 (8.7 %) and 42/370 (11.3%) patients, respectively. Nodal involvement was observed in 46/136 (33.8%), 8/24 (33.3%), 15/94 (15.9%), 4/42 (9.5%) and 1/81 (1.2%) patients with serous, undiffentiated, endometrioid, clear cell, and mucinous histology (p < .001). Via multivariate analysis, we observed that poor differentiated tumor, (FIGO grade 3), serous histology and bilateral tumors wereindependently associated with both pelvic and para-aortic nodal involvement (p < .01). The risk of presence of nodal involvement was calcutaed using a nomogram. Conclusion: Our data suggested that FIGO grade 3, serous and bilateral eEOC are at high risk of having disease harboring in the lymph nodes. After receiving external validation, our data will help to identify patients deserving comprehensive retroperitoneal staging.

The Impact of Androgen Receptor Expression on Endometrial Carcinoma Recurrence and Survival.

Endometrial carcinomas (ECs) are the most common gynecologic cancers in the western world. The impact of androgen receptor (AR) on clinicopathologic parameters of EC is not well studied. The aim of our study is to assess the role of AR expression in ECs and correlate its expression with estrogen (ER) and progesterone (PR). A retrospective review of 261 EC was conducted. H&E slides were reviewed and clinicopathologic parameters were analyzed. Immunohistochemical stains for AR, ER, and PR were performed on a tissue microarray. The hormonal expression was evaluated and the data were analyzed using the Fisher exact test and Kaplan-Meier survival analysis. Patients' age ranged from 31 to 91 (median=65 y). Type I EC included 202 endometrioid and 7 mucinous carcinoma, whereas type II included 34 serous, 16 carcinosarcoma, and 2 clear cell carcinoma. Although not significant, AR expression showed more frequent association with type I EC, early tumor stage (I-II), and low FIGO grade (1-2) EC. AR expression significantly correlated with absence of lymphovascular invasion (P=0.041) and decreased LN involvement (P=0.048). Patients with AR expression showed increased disease-free survival (208 vs. 165 mo, P=0.008) and late disease recurrence (P=0.009). AR expression had a positive significant correlation with PR (P<0.001) and ER (P=0.037) expression. AR might play a role as a prognostic marker for ECs.

Synchronous Primary Ovarian Mucinous Carcinoma and Endometrioid Endometrial Carcinoma : A rare case report.

Introduction: Synchronous tumours of female genital tract are a rare . The most common organs involved are ovary and endometrium. Endometrioid carcinoma is the most common malignancy detected in majority of cases . Synchronous cancers with dissimilar histology are a very rare phenomenon . We report a case of 51 year old lady with synchronous primary mucinous carcinoma of ovary and primary endometrioid endometrial carcinoma . Case report: a 51 year old lady presented with post menopausal bleeding and foul smelling vaginal discharge of 1 month duration . Her CA125 was elevated. Magnetic resonance imaging showed increased endometrial thickness and a12.5x10x9.3cm mass in the fundus of uterus suggestive of a leiomyoma along with and a 13.8x11.5x11cm mass in the left adnexa. Endometrial aspiration done showed Complex Hyperplasia with Atypia. Total abdominal hysterctomy and bilateral salphingoophorectomy along with lymphnode sampling was performed . The adnexal mass was pT1a pN0 cM0 grade 2 invasive mucinous carcinoma. The endometrial lesion was pT1b pN0 cM0 FIGO grade 2 endometrioid endometrial adenocarcinoma. Conclusion : Synchronous ovarian tumours of dissimilar histology is extremely rare and there are only a few reports of ovarian mucinous carcinoma with endometrioid endometrial carcinoma. DOI: 10.21276/APALM.1295

Compliance with adjuvant treatment guidelines in endometrial cancer: room for improvement in high risk patients

ObjectivesCompliance of physicians with guidelines has emerged as an important indicator for quality of care. We evaluated compliance of physicians with adjuvant therapy guidelines for endometrial cancer patients in the Netherlands in a population-based cohort over a period of 10years. MethodsData from all patients diagnosed with endometrial cancer between 2005 and 2014, without residual tumor after surgical treatment, were extracted from the Netherlands Cancer Registry (N=14,564). FIGO stage, grade, tumor type and age were used to stratify patients into risk groups. Possible changes in compliance over time and impact of compliance on survival were assessed. ResultsPatients were stratified into low/low-intermediate (52%), high-intermediate (21%) and high (20%) risk groups. Overall compliance with adjuvant therapy guidelines was 85%. Compliance was highest in patients with low/low-intermediate risk (98%, no adjuvant therapy indicated). The lowest compliance was determined in patients with high risk (61%, external beam radiotherapy with/without chemotherapy indicated). Within this group compliance decreased from 64% in 2005–2009 to 57% in 2010–2014. In high risk patients with FIGO stage III serous disease compliance was 55% (chemotherapy with/without radiotherapy indicated) and increased from 41% in 2005–2009 to 66% in 2010–2014. ConclusionWhile compliance of physicians with adjuvant therapy guidelines is excellent in patients with low and low-intermediate risk, there is room for improvement in high risk endometrial cancer patients. Eagerly awaited results of ongoing randomized clinical trials may provide more definitive guidance regarding adjuvant therapy for high risk endometrial cancer patients.

Risk factors for lymph node metastases in women with endometrial cancer: A population-based, nation-wide register study-On behalf of the Swedish Gynecological Cancer Group.

The role of lymphadenectomy in the management of early endometrial cancer remains controversial. In the recent ESMO-ESGO-ESTRO guidelines, lymphadenectomy is recommended for patients with endometrioid adenocarcinoma Grade 3 with deep myometrial invasion, but complete agreement was not achieved. In Sweden, DNA aneuploidy has been included as a high-risk factor. The aim of our study was to evaluate the impact of tumor histology, FIGO grade, DNA ploidy and myometrial invasion (MI) on occurrence of lymph node metastasis (LNM) in patients with endometrial cancer. The study design is a retrospective cohort study based on prospectively recorded register data. Endometrial cancer patients registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2015 with FIGO Stages I-III and verified nodal status were included. Data on DNA ploidy, histology, FIGO grade and MI were included in multivariable log-binomial regression analyses with LNM as dependent variable. 1,165 cases fulfilled the inclusion criteria. The multivariable analyses revealed increased risk of LNM in patients with tumors with MI ≥ 50% (risk ratio [RR] = 4.1; 95% confidence interval [CI] 3.0-5.6), nonendometrioid compared to endometrioid histology (RR 1.8; CI 1.4-2.4) and FIGO Grade 3 compared to Grade 1-2 tumors (RR 1.5; CI 1.1-2.0). No statistically significant association between DNA ploidy status and LNM was detected. This population-based, nation-wide study in women with endometrial cancer confirms a strong association between MI ≥ 50%, nonendometrioid histology and FIGO Grade 3, respectively, and LNM. DNA ploidy should not be included in the preoperative decision making of removing nodes or not.

CTNNB1 (beta-catenin) mutation identifies low grade, early stage endometrial cancer patients at increased risk of recurrence.

Although the majority of low grade, early stage endometrial cancer patients will have good survival outcomes with surgery alone, those patients who do recur tend to do poorly. Optimal identification of the subset of patients who are at high risk of recurrence and would benefit from adjuvant treatment has been difficult. The purpose of this study was to evaluate the impact of somatic tumor mutation on survival outcomes in this patient population. For this study, low grade was defined as endometrioid FIGO grades 1 or 2, while early stage was defined as endometrioid stages I or II (disease confined to the uterus). Next-generation sequencing was performed using panels comprised of 46–200 genes. Recurrence-free and overall survival was compared across gene mutational status in both univariate and multivariate analyses. 342 patients were identified, 245 of which had endometrioid histology. For grade 1–2, stage I–II endometrioid endometrial cancer patients, age (HR 1.07, 95% CI 1.03–1.10), CTNNB1 mutation (HR 5.97, 95% CI 2.69–13.21), and TP53 mutation (HR 4.07, 95% CI 1.57–10.54) were associated with worse recurrence-free survival on multivariate analysis. When considering endometrioid tumors of all grades and stages, CTNNB1 mutant tumors were associated with significantly higher rates of grade 1–2 disease, lower rates of deep myometrial invasion, and lower rates of lymphatic/vascular space invasion. When both TP53 and CTNNB1 mutations were considered, presence of either TP53 mutation or CTNNB1 mutation remained a statistically significant predictor of recurrence-free survival on multivariate analysis and was associated with a more precise confidence interval (HR 4.69, 95% CI 2.38–9.24). Thus, mutational analysis of a 2 gene panel of CTNNB1 and TP53 can help to identify a subset of low grade, early stage endometrial cancer patients who are at high risk of recurrence.

Abnormal mismatch repair and other clinicopathologic predictors of poor response to progestin treatment in young women with endometrial complex atypical hyperplasia and well-differentiated endometrial adenocarcinoma: a consecutive case series.

To report the response to progestin therapy in young women with endometrial complex atypical hyperplasia (CAH) or FIGO grade 1 endometrial adenocarcinoma (FIGO 1 EAC) based on clinicopathologic features, including abnormal DNA mismatch repair (MMR) by immunohistochemistry (IHC). Consecutive case series. Olive View-UCLA Medical Center in Sylmar, CA, USA, and Cedars-Sinai Medical Center in Los Angeles, CA, USA. Women ≤55 years old with CAH or FIGO 1 EAC. Response to progestin therapy in 84 consecutive patients was assessed based on clinicopathologic factors, including age, body mass index (BMI), initial histology, and IHC staining for MMR proteins. Rates of abnormal MMR protein expression and response to progestin therapy were determined. Six (7%) patients had abnormal IHC staining, of whom five (83%) had FIGO 1 EAC at initial diagnosis. Following progestin treatment, none of the endometrial lesions in patients with abnormal IHC for MMR proteins had resolution of hyperplasia or malignancy, in contrast to 41 (53%) with normal staining (P = 0.028). Age ≤40 years and initial lesion (CAH versus FIGO 1 EAC) were predictors of response to progestin; BMI was not. In this cohort, 7% of women ≤55 years of age with CAH or FIGO 1 EAC had loss of MMR proteins by IHC. These patients had a higher incidence of invasive cancer and a lower incidence of resolution with progestin therapy. Abnormal MMR protein expression predicts poor response to progestins in young women with CAH or FIGO 1 EAC.

Vanishing endometrial carcinoma in hysterectomy specimens: probable implications for fertility sparing management

Background/aim: The vanishing cancer phenomenon was first reported in radical prostatectomy specimens in the absence of neo-adjuvant treatment. Reported cases are mostly well-differentiated and low-volume tumors. A similar entity was described for hysterectomy specimens of patients with biopsy proven endometrial cancer (EC). In this study, we discuss the probable reasons for vanishing EC and long-term follow-up results of EC patients without residual tumors in hysterectomy specimens. Materials and methods: This study was carried at two institutions in Ankara, Turkey, in a retrospective design. The computerized databases of both institutions were searched for endometrioid type EC patients whose final pathological specimens failed to show any residual tumor. Results: We evaluated 38 endometrial biopsy confirmed EC patients with no residual tumor detected in the hysterectomy specimens among a total of 224 women (17%) with the disease confined to the endometrium. During the follow-up period, no recurrences were noted among the patients. Conclusion: It can be suggested that premenopausal women with FIGO grade 1 endometrioid type EC with MRI proven "absent myometrial invasion" would have a significant probability of having no residual tumor after endometrial biopsy without any further medical treatment.

Is lower uterine segment involvement a prognostic factor in endometrial cancer?

The purpose of this study is to investigate the prognostic significance of lower uterine segment (LUS) involvement in endometrial cancer (EC). We reviewed the patients who were operated at our institution between July 2007 and March 2015 with the diagnosis of EC. Tumors localized in the corpus and involving the LUS or localized entirely in the LUS formed Group A, while tumors in the uterine corpus without LUS involvement formed Group B. Clinicopathological characteristics and survival of the patients were compared in both groups. A total of 500 patients were included in the study. There were 139 patients who had tumors involving the LUS and formed Group A, while 361 patients with endometrial tumors in the uterine corpus without LUS involvement formed Group B. We did not detect a significant difference between survival of the patients in group A and group B (78 months vs. 87 months, respectively; P > 0.05). We found that LUS involvement was not an independent prognostic factor for poor survival, but it is associated with other poor prognostic factors such as deep myometrial invasion, uterine serosal involvement, lymphovascular space invasion, lymph node metastasis and higher FIGO grade.

Endometrium Kanserinde Prezentasyon Bulgusu Olarak Asetabulum Metastazı

Acetabulum is uncommon extraordinary place for endometrial cancer metastasis. Here we report a case of primary bone metastasis as initial presentation of the endometrial cancer. A 67 years old nulliparous Turkish woman admitted to the hospital with right hip pain. Magnetic resonance imaging was realized and a mass in size of 40x66 mm was reported in the posterior of the right acetabulum. Biopsy of the mass was taken and the result was recorded as metastatic adenocarcinoma. PET CT revealed that a mass of approximately 78x63 mm on the right acetabulum and a heterogeneous increase of F-18 FDG uptake (SUVmax: 11.8) was noticed. Further, irregular enlarged endometrial cavity and increased F-18 FDG involvement (SUVmax:13,4) were observed. Endometrial biopsy was applied and the result was reported as endometrial adenocarcinoma FIGO grade 2. In conclusion, endometrial biopsy should be included in the women patient's screening when investigated for metastatic bone adenocarcinoma.

The impact of lymphadenectomy on survival endpoints in women with early stage uterine endometrioid carcinoma: A matched analysis

ObjectivesThe role of pelvic lymphadenectomy (LA) in women with stage I endometrial carcinoma (EC) is controversial. The objective of this study is to investigate the prognostic impact of LA on survival endpoints in matched cohorts of women with stage I EC solely of endometrioid histology. Survival endpoints included recurrence-free (RFS), disease-specific (DSS) and overall survival (OS). Methods and materialsPatients with FIGO stage I EC who underwent hysterectomy with LA as part of their surgical staging between 1/1990 and 6/2015 were matched to a similar group that underwent hysterectomy without lymphadenectomy (NLA), based on stage, grade and adjuvant management. Univariate and multivariate modeling with Cox regression analysis was carried out for predictors of survival endpoints. Results870 women constituted the study cohort (435 in each group). Median number of dissected lymph node in the LA group was 9 (range, 5–75). There was no statistically significant difference between the two groups in regards to 5-year OS (87.2% for LA vs. 91.7% for NLA) (p=0.36), DSS 97.7% vs. 98% (p=0.54) and RFS (93.7% vs. 90% (p=0.08), respectively. Lymphadenectomy was not a predictor of any of the studied survival endpoints. On multivariate analysis for the entire cohort, older age, deep myometrial invasion and higher tumor grade were predictors of worse RFS. For DSS, higher tumor grade, lower uterine segment (LUS) involvement and FIGO stage IB were significant predictors of worse outcome. For OS, older age and LUS involvement were the only two independent predictors for shorter OS. ConclusionsAfter matching for FIGO stage, grade and adjuvant management, it appears that lymphadenectomy in women with stage I EC does not impact survival endpoints.

Endometrioid Endometrial Cancer: Concordance Between Preoperative and Final Surgical Histopathology

Purpose To compare the diagnostic accuracy of histopathological reporting of endometrial sampling with the final hysterectomy specimen histopathology in clinical stage 1 FIGO grade 1/2 endometrioid-type endometrial cancer.

Clinicopathologic and Immunohistochemical Characterization of Dedifferentiated Endometrioid Adenocarcinoma

Dedifferentiated endometrioid adenocarcinoma (DEAC) of the uterus or ovary is characterized by the coexistence of low-grade endometrioid adenocarcinoma and an undifferentiated carcinoma (UC) with solid sheets of medium-sized monotonous epithelial cells. This admixed carcinoma has not been widely recognized, because the solid areas of UC have usually been misdiagnosed as a solid form of FIGO grade 3 endometrioid adenocarcinoma. These tumors have been shown to be clinically aggressive; therefore, accurate diagnosis is necessary for proper patient management. We reviewed our experience with DEACs and compared them with grade 3 endometrioid carcinomas regarding their clinicopathologic, morphologic, and immunohistochemical features. Our results indicate that DEACs are clinically aggressive tumors presented at advanced stages with vascular invasions in 73% and lymph node metastases in 46%. Thirty-eight percent of cases also showed distal metastases. Clinical follow-up data revealed that all patients had either recurrent or metastatic diseases within 3 years of diagnosis, except 1 patient who remained disease free for 3 years after diagnosis. Morphologically, UC components of DEACs were composed of diffuse sheets/solid nests of medium-sized epithelial cells with scant to moderate cytoplasm, uniform vesicular nuclei, and inconspicuous nucleoli. Although UC components of DEACs are variably positive for cytokeratin, EMA, and ER, they are mostly negative for PAX8, except 1 case. Instead, well-differentiated components of DEACs and solid grade 3 endometrioid carcinoma retained all these markers. Our results indicate that DEACs exhibit significantly different clinicopathologic features from grade 3 endometrioid adenocarcinoma, and a combination of immunohistochemical stains can be helpful to differentiate them from each other.

Abstract 1793: POLE gene mutations confer good progression free survival in Asian women with FIGO grade 3 endometrioid endometrial carcinoma

Abstract Introduction: Endometrial carcinoma (EC) is the most common gynaecological cancer in developed countries. Mortality rates of patients with FIGO grade 3 endometrioid ECs are almost similar to that of uterine serous carcinoma and clear cell carcinoma. In 2013, the Cancer Tumour Genome Atlast (TGCA) identified POLE gene mutations in a subset of ECs, predominantly in the endometrioid subtype with high FIGO grade. While it has been suggested that POLE mutation confers good prognosis, the data remains conflicting. Our study aims to evaluate the association between the POLE gene mutations and progression free survival in Asian women with FIGO grade 3 endometrioid EC. Methods: Forty-five Asian patients diagnosed with FIGO Grade 3 endometrioid EC between 2009 and 2013 were included. Next generation sequencing (NGS) performed utilizing the Ion Torrent Personal Genome Machine (PGM) and custom designed AmpliSeq panel for formalin fixed embedded (FFPE) tissue was performed. Using the Ion Reporter, mutations with at least 10% allele frequency and present in the COSMIC database were deemed to be pathogenic. All other mutations, excluding silent mutations, were considered as variants of unknown significance (VUS). Survival curves for pathogenic somatic POLE mutated and wild-type tumors were estimated by Kaplan-Meier method and compared using logrank test. Results: All detected pathogenic and VUS POLE gene mutations were missense mutations. Our results provide further evidence to corroborate the mutation effect of POLE gene with 100% recurrence free survival in FIGO Grade 3 endometrioid EC patients with pathogenic POLE gene mutations, extends to South East Asian women as well (median follow-up POLE vs wild type; 52.5 vs 45; p = 0.2). Pathogenic somatic POLE gene mutations were present in 25.5% (12/45) patients with Grade 3 endometrioid EC. All were still alive at the time of censure with no reports of relapse following initial treatment. Three of these women harbored mutations outside exons 9 to 14 with one mutation listed as pathogenic in colorectal carcinomas. Among women without the pathogenic somatic POLE mutation, recurrence was seen in 24.2% (8/33) with 15.1% (5/33) subsequently dying of the disease. Conclusion: POLE gene mutations confer a good prognosis for FIGO grade 3 endometrioid EC and will be important in clinical decision making. POLE wild-type patients potentially show have closer follow-up and should be considered for newer targeted chemotherapeutic agents. Citation Format: Adele Wong, Chik Hong Kuick, Wai Loong Wong, Jill M. Tham, Sorsiah Mansor, Loh Eva, Sudhanshi Jain, Sock Hoai Chan, Sze Huey Tan, Shao Tzu Li, Nadkarni N. Vikas, Sung Hock Chew, Joanne Ngeow, Wanjin Hong. POLE gene mutations confer good progression free survival in Asian women with FIGO grade 3 endometrioid endometrial carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1793.

Vascular endothelial growth factor (VEGF) and cyclooxygenase 2 (COX 2) immunostaining in ovarian cancer.

Vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX 2) are markers of angiogenesis and potential therapeutic targets. Previous studies demonstrate that VEGF is upregulated in some ovarian cancers. The purpose of this study was to determine the correlation of VEGF and COX 2 staining with survival in ovarian cancer patients. One hundred forty-three consecutive patients with ovarian carcinoma underwent primary staging or cytoreduction prior to platinum-based chemotherapy. Their tumors were immunohistochemically stained for expression of VEGF and COX 2. FIGO stage, grade, cytoreduction status, and histology were also analyzed as prognostic factors. Twenty-seven patients had Stage I tumors, three Stage II, 87 Stage III, and 26 Stage IV. Median follow-up was 74 months (mean 79 months). One hundred nineteen patients (83.2%) had tumors that were positive for VEGF and 110 patients (76.9%) had tumors that were positive for COX 2. Patients with tumors staining positive for both VEGF and COX 2 (68.5%) had a significantly increased risk of dying from their ovarian cancer (Chi-square p = 0.011, Log rank p = 0.037). Multivariate logistic regression analysis revealed FIGO stage, grade, cytoreduction status, and VEGF/COX 2 expression to be independent prognostic indicators of survival. Conclusion: VEGF and COX 2 staining are frequently positive in ovarian cancer. Patients whose tumors are positive for both VEGF and COX 2 have a decreased survival. These patients may benefit from anti-angiogenesis targeted therapy.

Significant frequency of MSH2/MSH6 abnormality in ovarian endometrioid carcinoma supports histotype-specific Lynch syndrome screening in ovarian carcinomas.

Lynch syndrome screening in ovarian carcinoma is controversial. The aim of this study was to assess the frequency of deficient mismatch repair (dMMR) protein in a retrospective cohort enriched for non-high-grade serous carcinomas and its association with outcome within histological types. Tissue microarrays representing 612 ovarian carcinomas were tested for mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry. dMMR was detected in 13.8% of endometrioid and 2.4% of clear cell carcinomas, but not in other histological types. Within endometrioid carcinomas, 11 of 25 dMMR cases showed abnormal MLH1/PMS2, 10 cases showed abnormal MSH2/MSH6, and four cases showed only abnormal MSH6, indicating that at least 7.7% of endometrioid carcinomas have dMMR probably related to Lynch syndrome. The four dMMR clear cell carcinomas showed abnormal MSH2/MSH6 in three cases and only abnormal MSH6 in one case, all probably related to Lynch syndrome. Within endometrioid carcinomas, dMMR was significantly associated with age <50 years, synchronous endometrial endometrioid carcinoma, a higher CA125 level at diagnosis, higher FIGO grade, absence of ARID1A, and at least 20 CD8-positive intraepithelial lymphocytes per high-power field, but was not associated with cancer-specific death. Age <50 years, higher CA125 levels at diagnosis and at least 20 CD8-positive intraepithelial lymphocytes per high-power field remained significant after adjustment for multiple testing, but their sensitivity for identifying dMMR remained insufficient. Our data support the policy of histotype-specific Lynch syndrome screening in ovarian carcinoma confined to endometrioid and clear cell carcinomas.

Metabolic Determinants and Anthropometric Indicators Impact Clinical-pathological Features in Epithelial Ovarian Cancer Patients.

Background: Over the last twenty years, the efforts of the scientific community devoted to the comprehension and treatment of ovarian cancer have remained poorly remunerative, with the case-fatality ratio of this disease remaining disappointedly high. Limited knowledge of the basic principles regulating ovarian carcinogenesis and factors impacting the course of disease may significantly impair our ability to intervene in early stages and lessen our expectations in terms of treatment outcomes. In the present study, we sought to assess whether metabolic factors and anthropometric indicators, i.e., pre-treatment fasting glucose and body mass index, are associated with renown cancer related prognostic factors such as tumour stage and grade at diagnosis.Materials and Methods: Study participants were 147 women diagnosed with epithelial ovarian cancer and treated with platinum based regimens and/or surgery at the Regina Elena National Cancer Institute of Rome, Italy. Glucose levels were assessed at the institutional laboratories on venous blood collected in overnight fasting conditions and prior to any therapeutic procedure. Stage was coded according to the FIGO staging system based on the results of the diagnostic workup, while tumour grade was locally assessed by an expert pathologist. Participants' characteristics were descriptively analyzed for the overall study population and in a subgroup of 70 patients for whom data on body mass index (BMI) were available. FIGO stage and grade were compared by categories of pre-treatment fasting glucose defined upon the median value, i.e., 89 mg/dl. The association of interest was tested in regression models including BMI.Results: For the overall study population, patients in the lowest category of fasting glucose were significantly more likely to exhibit a FIGO stage III-IV at diagnosis compared with their counterpart in the highest glucose category (81.3 vs 66.7%, p: 0.021). Subgroup analysis in 70 patients with BMI data confirmed this association (81.5 vs 55.8, p: 0.049), which remained significant when tested in regression models including BMI (OR: 0.28 95% CI 0.086-0.89, p: 0.031). No relevant evidence emerged when testing the association between fasting glucose and tumour grade.Conclusions: In patients diagnosed with epithelial ovarian cancer, pre-treatment glucose levels appear to be inversely associated with FIGO stage. Further studies are warranted to eventually confirm and correctly interpret the implications of this novel finding.

Mutation spectrum of POLE and POLD1 mutations in South East Asian women presenting with grade 3 endometrioid endometrial carcinomas

ObjectiveSomatic POLE mutations have been found in a subset of endometrioid ECs particularly in FIGO grade 3 tumors while POLD1 mutations are reportedly rare in ECs. While it has been suggested that POLE mutation confers good prognosis, the data remains conflicting. Our study aims to determine the mutation spectrum of somatic and germline POLE and POLD1 gene mutations in South East Asian (SEA) women with FIGO grade 3 endometrioid ECs. MethodsForty-seven patients diagnosed with FIGO grade 3 endometrioid EC, diagnosed between 2009 and 2013 were included. Next generation sequencing (NGS) using formalin fixed embedded (FFPE) tissue was utilized to sequence tumor and matched normal tissue. Tumors were also assessed for other clinicopathologic and microsatellite status phenotype. Survival curves for pathogenic somatic POLE mutated and wild-type tumors were estimated by Kaplan–Meier method. ResultsPathogenic POLE (somatic or germline) and POLD1 (germline) mutations were detected in 29.7% (14/47) and 4.3% (2/47) patients, respectively. Three pathogenic germline mutations; one POLE and two POLD1 mutations were novel. Pathogenic germline and somatic POLE and POLD1 mutations were associated with 100% recurrence free survival. In contrast, among the wild-type POLE and POLD1 patients, 25% (8/32) had recurrence with 15.6% (5/32) subsequently dying of the disease. Somatic POLE-mutated tumors were more commonly associated with microsatellite stable (MSS) ECs (83% vs 49%; p=0.04) and peritumoral lymphocytic infiltration (75% vs 42%; p=0.05). All tumors with tumoral infiltrating lymphocytes exhibited peritumoral lymphocytic infiltrate but not vice versa. ConclusionMutations in POLE and POLD1 in SEA women with grade 3 endometrioid ECs are associated with improved recurrence free survival. Notably, germline mutations in either POLE/POLD1 were seen in 8.5% of patients who will require appropriate genetic counseling regarding risk of developing colorectal carcinoma and on the need for additional surveillance for colonic changes. MSS and peritumoral lymphocytic infiltration may be useful histological features for distinguishing POLE mutated grade 3 endometrioid ECs.

Age cut-off for reporting endometrial cells on a Papanicolaou test: 50 years may be more appropriate than 45 years.

The 2001 Bethesda System for Reporting Cervical Cytology includes documenting 'endometrial cells in women ≥40 years of age' (E40) to help identify endometrial carcinoma (EC) on a Papanicolaou (Pap) test. The 2014 Bethesda System for Reporting Cervical Cytology raises the threshold to ≥45 years of age (E45). As many of these women are menstruating, routine biopsy after E40, or even E45, may lead to unnecessary procedures for benign endometrial cells. Establishing a different age threshold in combination with other clinical findings may help to guide management. A retrospective chart review was performed on consecutive EC specimens and E40 Pap tests. Clinical, pathological data such as age, biopsy diagnosis, FIGO grade and the time of the last Pap test, Pap test diagnosis and resection diagnosis, depth of invasion, stage and metastases were recorded. Sixty-three EC cases had prior Pap smears, with the following diagnoses: negative for an intraepithelial lesion or malignancy (n = 27), atypical glandular cells, not otherwise specified (AGC, NOS) (n = 14), adenocarcinoma (n = 10) and E40 (n = 1; 51 years). Six hundred and forty-two E40 cases had 138 (21.5%) biopsies and/or hysterectomies. Out of the 138 cases, two (1.4%) had EC (both 51 years; postmenopausal), one had complex hyperplasia with atypia (52 years; abnormal uterine bleeding), and eight had hyperplasia without atypia. In asymptomatic women less than 50 years, E40 correlated with benign, non-hyperplastic endometrium. However, post-menopausal women with E40 had a risk of EC. Perhaps endometrial cells should only be reported in post-menopausal women or women greater than or equal to 50 years of age.

Uterine sarcomas.

Uterine sarcomas.