Work

Molecular subtypes and survival patterns of endometrial cancer in a South Indian cohort

Year: 2026

Type: article

Abstract: OBJECTIVE: This study investigates outcomes of The Cancer Genome Atlas (TCGA)-surrogate molecular types of endometrial cancer in South Indian patients, including polymerase epsilon (POLE)-mutated, mismatch repair-deficient (MMRd), p53 aberrant, and no specific molecular profile (NSMP) types. METHODS: The retrospective cohort, followed-up prospectively consisted of 151 patients from two institutions in Kerala, India: Government Medical College, Kozhikode, and MVR Cancer Center. The study spanned from January 1, 2016, to October 31, 2024. Sanger sequencing of the POLE gene (exons 9 and 13), TP53 (exons 5-8), CTNNB1, and PTEN genes, along with immunohistochemistry for mismatch repair (MMR) proteins, p53, estrogen receptor, and progesterone receptor, was performed to determine molecular types and associated variables. RESULTS: The study identified four subtypes: 39 POLE mutated (25.8%), 44 MMRd (29.1%), 29 p53 aberrant (19.2%), and 39 NSMP (25.8%). The 5-year recurrence-free survival (RFS) rates are POLE mutated (69%), MMRd (87%), p53abn (89%), and NSMP (64%) (P = 0.012). The study identified a "non-pathogenic" POLE-mutated subtype showing poor outcomes for overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS) (hazard ratios [HRs] for OS 5.45, P = 0.010; HR for DSS 4.83, P = 0.020; HR for RFS 4.12, P = 0.017) in multivariable analysis. Follow-up averaged 5.1 years. Estrogen receptor-positive low-grade endometrioid POLE-mutated tumors demonstrated excellent survival, while high-grade tumors negatively affected the POLE-mutated group. MMRd subtype, despite presenting in advanced stages with high-risk uterine factors, had excellent prognosis. The p53 aberrant group, predominantly with endometrioid histology and low-grade tumors, also showed good prognosis with standard treatment protocols. NSMP subtype revealed unfavorable outcome. Neither CTNNB1 mutation or ER PR status was noted to be a determinant of the poor outcome. Multiple-classifier tumors (>1 TCGA-surrogate type) were identified, with POLEmut-p53 being the largest group, showing characteristics similar to POLEmut. CONCLUSION: The study's findings diverge from prognostic implications of TCGA-surrogate molecular types, suggesting genetic diversity and ethnicity as potential outcome determinants in South Indian endometrial cancer patients.

Source: International Journal of Gynecology & Obstetrics