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Published on: September 12, 2019
Molecular subtypes and survival patterns of endometrial cancer in a South Indian cohort
Santhosh Kuriakose1, Dhananjayan Dhanasooraj2, Shiny Padinjarayil Manakkattu3
1Gynecologic Oncology Division, Department of Obstetrics and Gynecology, Government Medical College, Kozhikode (GMCK), Institute of Maternal and Child Health Block, Kozhikode, Kerala, India.
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.
