To investigate the risk factors for occult omental metastasis and the effect of omentectomy on the survival of type 2 endometrial cancer (EC) patients. This study enrolled patients who were diagnosed with high-risk (grade 3, serous, clear cell, undifferentiated, carcinosarcoma, or mixed type) EC between 2000 and 2021 and underwent surgery in our center. Data from 482 patients were analyzed retrospectively. Omentectomy was performed in 405 (84.0%) patients. Omental metastases were detected in 61 (12.7%) patients. Eighteen (29.5%) of these metastases were occult. Adnexal involvement, malignant cytology, and peritoneal spread were independent risk factors for omental metastasis. The 5-year overall survival (OS) rate was 59.5% in patients who underwent omentectomy and 64.7% in those who did not (P = 0.558). In patients with and without omental metastases, the overall 5-year OS rates were 34.9% and 63.5%, respectively (P < 0.001). The 5-year OS rates of patients with a normal omentum, gross tumors, and occult metastases were 63.5%, 26.9%, and 52.5%, respectively (P < 0.001). Omental metastases is not uncommon in type II endometrial cancer; approximately one third of patients have occult metastases. Factors - positive cytology, adnexal involvement, and peritoneal involvement are associated with higher probability of omental metastases.

Factors that stimulate the migration of fallopian tube epithelial (FTE)-derived high-grade serous ovarian cancer (HGSOC) to the ovary are poorly elucidated. This study characterized the effect of the ovarian hormone, activin A, on normal FTE and HGSOC. Activin A and TGFβ1 induced an epithelial-to-mesenchymal transition in murine oviductal epithelial (MOE) cells, but only activin A increased migration. The migratory effect of activin A was independent of Smad2/3 and required phospho-AKT, phospho-ERK, and Rac1. Exogenous activin A stimulated migration of the HGSOC cell line OVCAR3 through a similar mechanism. Activin A signaling inhibitors, SB431542 and follistatin, reduced migration in OVCAR4 cells, which expressed activin A subunits (encoded by INHBA). Murine superovulation increased phospho-Smad2/3 immunostaining in the FTE. In Oncomine, transcripts for the activin A receptors (ACVR1B and ACVR2A) were higher in serous tumors relative to the normal ovary, while inhibitors of activin A signaling (INHA and TGFB3) were lower. High expression of both INHBA and ACVR2A, but not TGFβ receptors or co-receptors, was associated with shorter disease-free survival in serous cancer patients. These results suggest activin A stimulates migration of FTE-derived tumors to the ovary.

OBJECTIVE: The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin.
METHODS: Nation-wide population-based study of women≥18years with histologically verified non-uterine serous cancer, included in the Swedish Quality Registry for primary cancer of the ovary, fallopian tube and peritoneum diagnosed 2009-2013. Relative survival (RS) was estimated using the Ederer II method. Simple and multivariable analyses were estimated by Poisson regression models.
RESULTS: Of 5627 women identified, 1246 (22%) had borderline tumors and 4381 had malignant tumors. In total, 2359 women had serous cancer; 71% originated in the ovary (OC), 9% in the fallopian tube (FTC), 9% in the peritoneum (PPC) and 11% at an undesignated primary site (UPS). Estimated RS at 5-years was 37%; for FTC 54%, 40% for OC, 34% for PPC and 13% for UPS. In multivariable regression analyses restricted to women who had undergone primary or interval debulking surgery for OC, FTC and PPC, site of origin was not independently associated with survival. Significant associations with worse survival were found for advanced stages (RR 2.63, P<0.001), moderate (RR 1.90, P<0.047) and poor differentiation (RR 2.20, P<0.009), neoadjuvant chemotherapy (RR1.33, P<0.022), residual tumor (RR 2.65, P<0.001) and platinum single (2.34, P<0.001) compared to platinum combination chemotherapy.
CONCLUSIONS: Survival was poorer for serous cancer at UPS than for ovarian, fallopian tube and peritoneal cancer. Serous cancer at UPS needs to be addressed when reporting and comparing survival rates of ovarian cancer.

OBJECTIVE: The lack of randomized clinical data pertaining to optimal surgery and adjuvant treatment in women with high-risk histotypes of endometrial cancer has resulted in selective management based on institutional policies. The objective of this study was to assess differences in treatment strategies and their outcomes among various institutions.
METHODS: High-risk endometrial cancer cases (2000-2012) with corresponding clinicopathologic data were collected from 7 academic cancer centers. Histotypes included grade 3 endometrioid (EC3), serous (ESC), clear cell (CCC) and carcinosarcoma (CS). Associations with overall survival were performed using Cox proportional hazard regression.
RESULTS: 1260 patients treated between 2000 and 2012 were included in the study: 398 EC3, 449 ESC, 91 CCC, 236 CS and 83 \'other\'. The use of adjuvant chemotherapy, adjuvant radiation, and extent of surgical staging were statistically different among the 7 centers (P<0.001). Histotype was independently associated with overall survival (OS) in patients with stage 1 and 2 disease who underwent surgical staging (P=0.0324). Adjuvant radiation was associated with improved OS for EC3 and CCC and adjuvant chemotherapy was associated with improved OS for ESC and CS. There was a high rate of recurrence (17.8% and 21.4%) in completely staged, stage 1A patients with ESC and CS respectively.
CONCLUSIONS: There exists a wide variation in practice and outcomes for high-risk histotypes of endometrial cancer. The relative impact of adjuvant therapy appears to be histotype dependent and prospective studies examining adjuvant treatment in high-risk histotypes should use caution combining them together.

OBJECTIVE: The fallopian tube has been implicated as the primary origin of pelvic serous cancers. We proposed to determine the survival outcomes of serous tubal, ovarian, peritoneal, and uterine cancer patients.
METHODS: Data were obtained from the National Cancer Institute between 2004 and 2009. Kaplan-Meier and Cox proportional hazards models were used for analysis.
RESULTS: Of 12,336 high-grade serous cancer patients, 563 were tubal (TC), 8560 ovarian (OC), 1037 primary peritoneal (PPC), and 2176 uterine cancer (USC). The median ages of these patients were 63 vs 62 vs 67 vs 68 years, respectively. The majority were white (89% vs 88% vs 91% vs 74%). The overall 5 year, disease-specific survival was 37%. The survivals of those with TC, OC, PPC, and USC were 50%, 37%, 26%, and 40% (P < .01). There was no detailed staging on PPC cancers. Adjusted for stage, the survival of those with stage I, II, III, and IV TC were 73%, 62%, 44%, and 22% (P < .01), OC were 83%, 64%, 34%, and 15% (P < .01), and USC were 88%, 72%, 55%, and 17% (P < .01). On multivariate analysis, younger age, white race, earlier stage, and tubal origin were independent predictors for improved survival.
CONCLUSIONS: In advanced-staged serous cancer patients, tubal cancer patients have better survivals compared with ovarian, peritoneal, and uterine cancer.

OBJECTIVE: This study computed the risk of clinically silent adnexal neoplasia in women with germ-line BRCA1 or BRCA2 mutations (BRCA(m+)) and determined recurrence risk.
METHODS: We analyzed risk reduction salpingo-oophorectomies (RRSOs) from 349 BRCA(m+) women processed by the SEE-FIM protocol and addressed recurrence rates for 29 neoplasms from three institutions.
RESULTS: Nineteen neoplasms (5.4%) were identified at one institution, 9.2% of BRCA1 and 3.4% of BRCA2 mutation-positive women. Fourteen had a high-grade tubal intraepithelial neoplasm (HGTIN, 74%). Mean age (54.4) was higher than the BRCA(m+) cohort without neoplasia (47.8) and frequency increased with age (p < 0.001). Twenty-nine BRCA(m+) patients with neoplasia from three institutions were followed for a median of 5 years (1-8 years.). One of 11 with HGTIN alone (9%) recurred at 4 years, in contrast to 3 of 18 with invasion or involvement of other sites (16.7%). All but two are currently alive. Among the 29 patients in the three institution cohort, mean ages for HGTIN and advanced disease were 49.2 and 57.7 (p = 0.027).
CONCLUSIONS: Adnexal neoplasia is present in 5-6% of RRSOs, is more common in women with BRCA1 mutations, and recurs in 9% of women with HGTIN alone. The lag in time from diagnosis of the HGTIN to pelvic recurrence (4 years) and differences in mean age between HGTIN and advanced disease (8.5 years) suggest an interval of several years from the onset of HGTIN until pelvic cancer develops. However, some neoplasms occur in the absence of HGTIN.

It is currently hoped that deaths from extra-uterine high-grade serous cancer (HGSC) will be reduced via opportunistic salpingectomy in healthy women. Accumulated data implicate the fimbria as a site of origin and descriptive molecular pathology and experimental evidence strongly support a serous carcinogenic sequence in the Fallopian tube. Both direct and indirect (\'surrogate\') precursors suggest that the benign tube undergoes important biological changes after menopause, acquiring abnormalities in gene expression that are often shared with malignancy, including PAX2, ALDH1, LEF1, RCN1, RUNX2, beta-catenin, EZH2, and others. However, the tube can be linked to only some HGSCs, recharging arguments that nearby peritoneum/ovarian surface epithelium (POSE) also hosts progenitors to this malignancy. A major sticking point is the difference in immunophenotype between POSE and Müllerian epithelium, essentially requiring mesothelial to Müllerian differentiation prior to or during malignant transformation to HGSC. However, emerging evidence implicates an embryonic or progenitor phenotype in the adult female genital tract with the capacity to differentiate, normally or during neoplastic transformation. Recently, a putative cell of origin for cervical cancer has been identified in the squamo-columnar (SC) junction, projecting a model whereby Krt7+ embryonic progenitors give rise to immunophenotypically distinct progeny under stromal influences via \'top down\' differentiation. Similar differentiation can be seen in the endometrium with a parallel in juxtaposed mesothelial and Müllerian differentiation in the ovary. Abrupt mesothelial-Müllerian transitions remain to be proven, but would explain the rapid evolution, short asymptomatic interval, and absence of a defined epithelial starting point in many HGSCs. Resolving this question will require accurately distinguishing progenitor from progeny tumour cells in HGSC and pinpointing where initial transformation and trans-differentiation occur, whether in the tube or POSE. Both will be critical to expectations from prophylactic salpingectomy and future approaches to pelvic serous cancer prevention.