Analysis of patients with endometrial carcinoma using the ProMise classifier: a pilot study from India.

BACKGROUND: Molecular subtyping of endometrial carcinomas (EC) has been shown to classify tumors into prognostically relevant groups. Characterizing EC with a limited number of markers viz., POLE mutations, p53 mutations, and MMR status, can provide valuable information. DESIGN: Paraffin sections of a cohort of 48 EC from a tertiary care center were characterized for the above-mentioned molecular markers and analyzed in the context of survival. METHODS: Formalin fixed paraffin embedded tissues from 48 EC were characterized for POLE mutations by Sanger sequencing (exons 9-14), for MMR (MLH1, MH2, MSH6) using immunohistochemistry (IHC) and copy number (high/low) using p53 IHC. Mutational status was integrated along with the clinicopathological details and survival analysis performed. RESULTS: Eleven (22.9%) patients were MMR deficient, 3 (6.3%) had POLE mutation, while 2 (4.1%) had both POLE and P53 mutations (regarded as multiple classifiers). Twelve (25%) patients were found to have P53 mutations, while the remaining 20 (41.7%) had no specific molecular profile (NSMP). Median follow-up duration was 43.5 (2-62) months with 8 recurrences and 9 deaths. Tumors with POLE mutation had the most favorable prognosis followed by the NSMP and the MMR mutated group while the P53 and multiple classifier groups had the worst prognosis in terms of OS (Log-rank p: 0.006) and PFS (Log-rank p: 0.001). CONCLUSION: The integration of molecular-clinicopathologic data for endometrial cancer classification, through cost-effective, clinically applicable assays appears to be a highly objective tool that can be adopted even in resource-limited settings. It has the potential to cause a shift in the paradigm of EC pathology and management practice.

Endometriosis and malignancy: The intriguing relationship.

OBJECTIVE: To determine the prevalence and study the association of ovarian, uterine, and breast cancers with endometriosis. METHODS: A cross-sectional study of all women with a tissue-proven diagnosis of endometriosis postoperatively in a tertiary care hospital between January 1, 2010, and December 31, 2019, was conducted to determine the prevalence of coexistent malignancy. Patient details were obtained from electronic clinical records. Univariate analysis followed by multivariate analysis was done to find independent risk factors associated with malignancy. RESULTS: Out of 800 patients, 104 (13.0%) were found to have coexistent malignancy: ovarian (50, 6.2%); endometrial (33, 4.1%); synchronous ovarian and endometrial (7, 0.9%); and breast (14, 1.8%). Increasing age (odds ratio [OR] 1.13; 95% confidence interval [CI] 1.09-1.16), higher levels of cancer antigen 125 (CA 125) (OR 1.002; 95% CI 1.001-1.005), postmenopausal status (OR 6.2; 95% CI 2.0-19.2), duration of endometriosis over 5 years (OR 4.7; 95% CI 2.5-9.0), and endometriomas larger than 8 cm (area under the curve 0.83) were predictive of coexistent malignancy. CONCLUSION: Endometriosis is associated with an increased risk of ovarian, endometrial, and breast malignancy. Increasing age, postmenopausal status, higher levels of CA 125, larger endometrioma, and long-standing disease are predictive risk factors.