Molecular Evaluation of Endometrial Dedifferentiated Carcinoma, Endometrioid Carcinoma, Carcinosarcoma, and Serous Carcinoma Using a Custom-Made Small Cancer Panel

It is often difficult to histologically differentiate among endometrial dedifferentiated carcinoma (DC), endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma (CS) due to the presence of solid components. In this study, we aimed to categorize these carcinomas according to The Cancer Genome Atlas (TCGA) classification using a small custom-made cancer genome panel (56 genes and 17 microsatellite regions) for integrated molecular diagnosis. A total of 36 endometrial cancer cases with solid components were assessed using IHC, next-generation sequencing (NGS), and the custom-made panel. Among 19 EC cases, six were categorized as MMR-deficient (MMR-d) and eight were classified as having a nonspecific molecular profile. Three EC cases were classified as POLE mutation (POLEmut)-type, which had a very high tumor mutation burden (TMB) and low microsatellite instability (MSI). Increased TMB and MSI were observed in all three DC cases, classified as MMR-d with mutations in MLH1 and POLD1. Except for one case classified as MMR-d, all SC cases exhibited TP53 mutations and were classified as p53 mutation-type. SC cases also exhibited amplification of CCND1, CCNE1, and MYC. CS cases were classified as three TCGA types other than the POLEmut-type. The IHC results for p53 and ARID1A were almost consistent with their mutation status. NGS analysis using a small panel enables categorization of endometrial cancers with solid proliferation according to TCGA classification. As TCGA molecular classification does not consider histological findings, an integrated analytical procedure including IHC and NGS may be a practical diagnostic tool for endometrial cancers.

Age-Specific Trend and Birth Cohort Effect on Different Histologic Types of Uterine Corpus Cancers

To evaluate the uterine corpus cancer incidence rates, age-specific trends and birth cohort patterns by different histologic types. From the Taiwan Cancer Registry, we identified women with a primary diagnosis of uterine corpus cancer (n=28 769) from1998 to 2017. We analyzed the incidences, stages of disease at diagnosis and prognostic factors in endometrioid and non-endometrioid carcinoma. During the study period, uterine corpus cancer incidence rates increased over time from 5.3 to 15.21 per 100 000 woman-years. Incidence trends for endometrioid carcinoma increased in all age groups and the rise was steeper in women age 40 years and younger. For non-endometrioid carcinomas, incidence rates increased in women over 50 years. Women diagnosed after 2013 had significantly better cancer-specific survival (CSS) (hazard ratio [HR] =0.81, 95% confidence interval [CI] 0.73-0.89) compared with those at the period of 2009-2012. CSS also improved in stage I (HR=0.81, 95% CI 0.49-0.63) and stage III (HR 0.90, 95% CI 0.58-0.72) endometrioid carcinomas after 2013. Whereas CSS remained unchanged for non-endometrioid carcinomas. We found the incidences of both endometrioid and non-endometrioid carcinomas continued to increase among contemporary birth cohorts. Etiologic research is mandatory to explain the causes for these trends.

A Case of Endometrial Carcinosarcoma Containing Sertoliform Endometrioid Carcinoma Component

Carcinosarcomas (CSs) of the endometrium have admixture of malignant epithelial and mesenchymal components. The carcinomatous component exhibit endometrioid, serous, or clear cell differentiation, or are undifferentiated. CSs are considered homologous or heterologous according to the type of sarcomatous component. Sertoliform endometrioid carcinomas (SECs) of the endometrium which comprise a rare subtype of endometrial cancer, typically occur in the ovary. SECs as a carcinomatous component of CS of the endometrium have not been reported. Here, we report an endometrial carcinosarcoma that contains an SEC component. An 88-year-old female presented to a clinic with atypical genital bleeding. She was referred to our hospital and underwent total hysterectomy, bilateral adnexectomy and partial omentectomy due to endometrial carcinoma. Gross examination revealed a polypoid mass in the uterine cavity with massive myometrial invasion. Histologically, the tumor was a high-grade endometrioid carcinoma. In addition to an ordinary conventional endometrioid carcinoma, approximately 30% of the area exhibited sex cord-like pattern and contained small hollow tubules, anastomosing cords and trabeculae, and tightly packed nests. Immunohistochemically, the SEC component showed diffuse p53 staining. Sex cord-like area, especially the solid area, showed positive staining for EMA, vimentin, α-inhibin, CD99, calretinin, p53, CD56, synaptophysin, and chromogranin A, which is a staining pattern similar to that previously reported SEC of the endometrium. Diminished membranous and positive cytoplasmic staining for β-catenin was observed. This is the first case report of an endometrial carcinosarcoma containing an SEC component. SECs of the endometrium might exhibit sex cord-like differentiation in contrast to SECs of the ovary, which do not exhibit sex cord differentiation.

RISK FACTORS FOR ESTROGEN EXPOSURE IN VARIOUS GRADES OF ENDOMETRIOID CARINOMA

Background: Incidence endometrial cancer in Southeast Asia it is estimated that 41% of new cases emerge. The incidence of endometrial cancer in Dr. Soetomo General Hospital has increased every year. In 2016 there were 119 new cases of endometrial cancer and in 2017 there were 160 cases. 75%-80% is type I endometrial cancer (endometrioid carcinoma). Risk factors for estrogen exposure (early menarche, parity, obesity) are risk factors for endometrial cancer. The prognosis of endometrial cancer depends on the grade. This study aims to determine differences in risk factors for estrogen exposure in various grades of type I endometrial cancer (endometrioid carcinoma) in the Poli Onkologi Satu Atap Dr. Soetomo General Hospital Surabaya. Methods: the research method was analytic observational with cross-sectional design. Sample size of 40 medical records was taken by total sampling technique. Research variables include age of menarche, parity, BMI, and grade of endometrial cancer. The instrument used was a data collection sheet and medical records. Data analysis using chi-square test. Results: The results showed 52% patients were grade 1-2, there were 95% of menarche patients in the age range of 12-14 years, 62.5% patients had parity of 1-2 and 52% patients, BMI was underweight-normal category. Test results based on early menarche did not show significant differences between grades 1-2 and grade 3 in endometrioid carcinoma (p = 0.168). Likewise, parity in various grades of endometrial cancer type I (endometrioid carcinoma) there was no significant difference (p = 0.220) and BMI also no significant difference (p = 0.987). Conclusions: risk factors for estrogen exposure which include menarche, parity, obesity do not make a significant differences to the grades of endometrioid carcinoma.