Prognostic stratification of endometrial cancers with high microsatellite instability or no specific molecular profile.

Objective: To identify high-risk disease in clinicopathologic low-risk endometrial cancer (EC) with high microsatellite instability (MSI-H) or no specific molecular profile (NSMP) and therapeutic insensitivity in clinicopathologic high-risk MSI-H/NSMP EC.

Methods: We searched The Cancer Genome Atlas for DNA sequencing, RNA expression, and surveillance data regarding MSI-H/NSMP EC. We used a molecular classification system of and expression and sequence variations in , , or (ECPPF) to prognostically stratify MSI-H/NSMP ECs.

ECPPF (E2F1, CCNA2, POLE, PPP2R1A, FBXW7) stratification: Profiling high-risk subtypes of histomorphologically low-risk and treatment-insensitive endometrioid endometrial cancer.

In endometrial cancer, occult high-risk subtypes (rooted in histomorphologically low-risk disease) with insensitivity to adjuvant therapies impede improvements in therapeutic efficacy. Therefore, we aimed to assess the ability of molecular high-risk (MHR) and low-risk (MLR) ECPPF (E2F1, CCNA2, POLE, PPP2R1A, FBXW7) stratification to profile recurrence in early, low-risk endometrioid endometrial cancer (EEC) and insensitivity to platinum-based chemotherapy or radiotherapy (or both) in high-risk EEC. Using The Cancer Genome Atlas endometrial cancer database, we identified 192 EEC cases with available DNA sequencing and RNA expression data.

Ten years of live surgical broadcast at Charité-MAYO conferences (2010-2019): a systematic evaluation of the surgical outcome.

Objective: The international Charité-MAYO Conference aims to promote international dialog on diagnostics, management, scientific breakthroughs, and state-of-the-art surgical procedures in gynecology and gynecologic oncology and senology. Live surgeries are a fundamental tool of interdisciplinary and international exchange of experts in their respective fields. Currently, there is a controversial and emotional debate about the true value, risks, and safety of live surgical broadcasts.

PP2A and E3 ubiquitin ligase deficiencies: Seminal biological drivers in endometrial cancer.

Objective: PI3K-AKT pathway mutations initiate a kinase cascade that characterizes endometrial cancer (EC). As kinases seldom cause oncogenic transformation without dysregulation of antagonistic phosphatases, pivotal interactions governing this pathway were explored and correlated with clinical outcomes.

Methods: After exclusion of patients with POLE mutations from The Cancer Genome Atlas EC cohort with endometrioid or serous EC, the study population was 209 patients with DNA sequencing, quantitative gene-specific RNA expression, copy number variation (CNV), and surveillance data available.

Association of a novel endometrial cancer biomarker panel with prognostic risk, platinum insensitivity, and targetable therapeutic options.

During the past decade, the age-adjusted mortality rate for endometrial cancer (EC) increased 1.9% annually with TP53 mutant (TP53-mu) EC disproportionally represented in advanced disease and deaths. Therefore, we aimed to assess pivotal molecular parameters that differentiate clinical outcomes in high- and low-risk EC.

Risk assessment of endometrial cancer and endometrial intraepithelial neoplasia in women with abnormal bleeding and implications for clinical management algorithms.

Background: Most endometrial cancer cases are preceded by abnormal uterine bleeding, offering a potential opportunity for early detection and cure of endometrial cancer. Although clinical guidelines exist for diagnostic workup of abnormal uterine bleeding, consensus is lacking regarding optimal management for women with abnormal bleeding to diagnose endometrial cancer.

Objective: We report the baseline data from a prospective clinical cohort study of women referred for endometrial evaluation at the Mayo Clinic, designed to evaluate risk stratification in women at increased risk for endometrial cancer.

Combining copy number, methylation markers, and mutations as a panel for endometrial cancer detection via intravaginal tampon collection.

Objective: We aimed to assess whether endometrial cancer (EC) can be detected in shed DNA collected with vaginal tampon by analyzing copy number, methylation markers, and mutations.

Methods: Tampons were collected prior to hysterectomy from 38 EC patients and 28 women with benign indications. Extracted tampon DNA underwent the following: 1) low-coverage whole genome sequencing (LC-WGS) to assess copy number, 2) pyrosequencing to measure percent promotor methylation of HOXA9, RASSF1, and CDH13 and 3) next generation sequencing (NGS) to identify mutations in 19 genes associated with EC identified through The Cancer Genome Atlas.

A prospective clinical cohort study of women at increased risk for endometrial cancer.

Objective: To evaluate endometrial cancer (EC) risk assessment and early detection strategies in high-risk populations, we designed a large, prospective cohort study of women undergoing endometrial evaluation to assess risk factors and collect novel biospecimens for future testing of emerging EC biomarkers. Here we report on the baseline findings of this study.

Methods: Women aged ≥45 years were enrolled at the Mayo Clinic from February 2013-June 2018.

Comparing risk stratification criteria for predicting lymphatic dissemination in endometrial cancer.

Objective: To compare two published risk stratification models (Milwaukee Model vs. Mayo Criteria) to predict lymphatic dissemination (LD) in endometrioid endometrial cancer (EC).

Methods: Patients with stage I-III EC undergoing surgery from 1/1/2004-9/30/2013 were retrospectively reviewed and classified as low-risk vs at-risk for LD using two independent risk models.

Uterine serous carcinoma: Reassessing effectiveness of platinum-based adjuvant therapy.

Objective: Two randomized trials failed to demonstrate efficacy of platinum-based chemotherapy (PbCT) for uterine serous carcinoma (USC). Our objective was to reassess the value of PbCT for patients with microscopic residuum (R0).

Methods: Progression-free survival (PFS) after surgery was analyzed for 409 patients and correlated with adjuvant therapies: vaginal brachytherapy (VBRT), external beam radiotherapy (EBRT), PbCT, or combinations.

Primary brain metastases of endometrial cancer: A report of 18 cases and review of the literature.

Objective: To present a series of brain metastases from endometrial cancer (EC) and describe a comprehensive review of the literature.

Methods: We retrospectively reviewed medical records of 1) patients with cerebral dissemination of EC treated at Mayo Clinic from 1984 to 2001 and 2) all patients referred for treatment of primary brain metastases after primary treatment for EC elsewhere. We also reviewed published case reports and case series describing cerebral spread of EC.

Pancreaticoduodenectomy in optimal primary cytoreduction of epithelial ovarian cancer: A case report and review of the literature.

•Aggressive multi-organ resection of epithelial ovarian cancer (EOC) at the time of primary cytoreduction improves patient survival.•We describe pancreaticoduodenectomy (Whipple procedure) as an efficacious tool for optimal cytoreduction in bulky upper abdominal EOC.

Risk-adjusted outcomes in elderly endometrial cancer patients: implications of the contrasting impact of age on progression-free and cause-specific survival.

Objective: To reexamine the tenet that advanced age independently impacts progression-free and cause-specific survival in patients with endometrial cancer (EC).

Methods: Patients undergoing surgery for stages I-IIIC EC between 1999 and 2008 were stratified by age (<70 vs ≥70years). Three propensity score (PS) methods were utilized to adjust for confounding risk factors.

Microarray analysis on gene regulation by estrogen, progesterone and tamoxifen in human endometrial stromal cells.

Epithelial stromal cells represent a major cellular component of human uterine endometrium that is subject to tight hormonal regulation. Through cell-cell contacts and/or paracrine mechanisms, stromal cells play a significant role in the malignant transformation of epithelial cells. We isolated stromal cells from normal human endometrium and investigated the morphological and transcriptional changes induced by estrogen, progesterone and tamoxifen.

Detection of endometrial cancer via molecular analysis of DNA collected with vaginal tampons.

Objective: We demonstrate the feasibility of detecting EC by combining minimally-invasive specimen collection techniques with sensitive molecular testing.

Methods: Prior to hysterectomy for EC or benign indications, women collected vaginal pool samples with intravaginal tampons and underwent endometrial brushing. Specimens underwent pyrosequencing for DNA methylation of genes reported to be hypermethylated in gynecologic cancers and recently identified markers discovered by profiling over 200 ECs.

Distribution and volume of extrauterine disease in uterine serous carcinoma: is minimally invasive surgery a suitable approach?

Objective: Minimally invasive surgery (MIS) is the preferred technique for managing endometrial cancer. Given that uterine serous carcinoma (USC) has a predilection for multiquadrant peritoneal dissemination, our objective was to estimate the potential risk for overlooking occult peritoneal spread with the use of MIS.

Methods: A single-institution, retrospective review was conducted of patients who underwent primary surgical staging for endometrial cancer via laparotomy between 1999 and 2008.

Prognostic and therapeutic relevance of molecular subtypes in high-grade serous ovarian cancer.

Molecular classification of high-grade serous ovarian cancer (HGSOC) using transcriptional profiling has proven to be complex and difficult to validate across studies. We determined gene expression profiles of 174 well-annotated HGSOCs and demonstrate prognostic significance of the prespecified TCGA Network gene signatures. Furthermore, we confirm the presence of four HGSOC transcriptional subtypes using a de novo classification.

Risk-scoring models for individualized prediction of overall survival in low-grade and high-grade endometrial cancer.

Objective: Overall survival (OS) in endometrial cancer (EC) is dependent on patient-, disease-, and treatment-specific risk factors. Comprehensive risk-scoring models were developed to estimate OS in low-grade and high-grade EC.

Methods: Patients undergoing primary surgery for EC from 1999 through 2008 were stratified histologically according to the International Federation of Gynecology and Obstetrics (FIGO) as either (i) low grade: grades 1 and 2 endometrioid EC or (ii) high grade: grade 3, including non-endometrioid EC.

Discovery and validation of methylation markers for endometrial cancer.

The prognosis of endometrial cancer is strongly associated with stage at diagnosis, suggesting that early detection may reduce mortality. Women who are diagnosed with endometrial carcinoma often have a lengthy history of vaginal bleeding, which offers an opportunity for early diagnosis and curative treatment. We performed DNA methylation profiling on population-based endometrial cancers to identify early detection biomarkers and replicated top candidates in two independent studies.

Efficacy of contemporary chemotherapy in stage IIIC endometrial cancer: a histologic dichotomy.

Background: Treatment failures in stage IIIC endometrial carcinoma (EC) are predominantly due to occult extrapelvic metastases (EPM). The impact of chemotherapy on occult EPM was investigated according to grade (G), G1/2EC vs G3EC.

Methods: All surgical-stage IIIC EC cases from January 1, 1999, through December 31, 2008, from Mayo Clinic were included.

HE4 transcription- and splice variants-specific expression in endometrial cancer and correlation with patient survival.

We investigated the HE4 variant-specific expression patterns in various normal tissues as well as in normal and malignant endometrial tissues. The relationships between mRNA variants and age, body weight, or survival are analyzed. ICAT-labeled normal and endometrial cancer (EC) tissues were analyzed with multidimensional liquid chromatography followed by tandem mass spectrometry.

The impact of perioperative packed red blood cell transfusion on survival in epithelial ovarian cancer.

Objective: Perioperative packed red blood cell transfusion (PRBCT) has been implicated as a negative prognostic marker in surgical oncology. There is a paucity of evidence on the impact of PRBCT on outcomes in epithelial ovarian cancer (EOC). We assessed whether PRBCT is an independent risk factor of recurrence and death from EOC.

Prospective assessment of the prevalence of pelvic, paraaortic and high paraaortic lymph node metastasis in endometrial cancer.

Objective: To prospectively define the prevalence of lymph node metastasis (LNM) in at risk endometrial cancer (EC).

Methods: From 2004 to 2008, frozen section based Mayo Criteria prospectively identified patients "not at-risk" of LNM (30% EC population; grade I/II, <50% myometrial invasion and tumor diameter ≤ 2 cm) where lymphadenectomy was not recommended. The remaining 70% EC cohort was considered "at-risk" of LNM; where a systematic pelvic and infrarenal paraaortic lymphadenectomy was recommended.