High prevalence of "non-pathogenic" POLE mutation with poor prognosis in a cohort of endometrial cancer from South India.

Autor: Kuriakose S; Gynecologic Oncology Division, Department of Obstetrics and Gynecology, Government Medical College, Kozhikode, Kerala, India., Dhanasooraj D; Multidisciplinary Research Unit, Government Medical College, Kozhikode, Kerala, India., Shiny PM; Department of Pathology, Government Medical College, Kozhikode, Kerala, India., Shammy S; Multidisciplinary Research Unit, Government Medical College, Kozhikode, Kerala, India., Sona VP; Multidisciplinary Research Unit, Government Medical College, Kozhikode, Kerala, India., Manjula AA; Department of Pathology, Government Medical College, Kozhikode, Kerala, India., Ramachandran A; Gynecologic Oncology Division, Department of Obstetrics and Gynecology, Government Medical College, Kozhikode, Kerala, India., Vijaykumar B; Department of Obstetrics and Gynecology, Government Medical College, Kozhikode, Kerala, India., Susan N; Department of Obstetrics and Gynecology, Government Medical College, Kozhikode, Kerala, India., Dinesan M; Department of Radiation Oncology, Tertiary Cancer Care Center, Government Medical College, Kozhikode, Kerala, India., Sankar UV; MVR Cancer Centre & Research Institute, Kozhikode, Kerala, India., Ramachandran K; Department of Pathology, MVR Cancer Centre & Research Institute, Kozhikode, Kerala, India., Sreedharan PS; Department of Medical Oncology, MVR Cancer Centre & Research Institute, Kozhikode, Kerala, India.
Jazyk: angličtina
Zdroj: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics [Int J Gynaecol Obstet] 2024 Sep; Vol. 166 (3), pp. 1263-1272. Date of Electronic Publication: 2024 Apr 03.
DOI: 10.1002/ijgo.15486
Abstrakt: Objective: The Cancer Genome Atlas (TCGA) project identified favorable prognosis regarding the ultra-mutated endometrial cancer (EC) subtype linked to polymerase epsilon gene (POLE) mutations. This study investigated POLE mutations in EC of Indian patients.
Methods: This retrospective analytical study was conducted between January 2016 and January 2023 at the Government Medical College, Kozhikode, and the MVR Cancer Center, Kozhikode, Kerala. Sanger sequencing of POLE gene exons 9 and 13 in 151 EC patients was carried out to analyze the relationship between mutations and epidemiological factors, clinicopathologic features, and treatment outcomes.
Results: Among 151 cases enrolled, 39 were unique POLE-mutated cases. Significant associations were high-grade tumors, myometrial invasion >50%, and Lymph-vascular space invasion (LVSI). The median follow-up was 40 months (95% confidence interval [CI], 34-46). A lower mean disease-specific survival (DSS) of 51.7 months (95% CI, 43.7-59.6) was noted in the POLE-mutated group compared with 72.11 months (95% CI, 67.60-76.62) for the POLE wild-type. A statistically significant hazard ratio (HR) of 2.683 for DSS in the POLE-mutated group was noted. In advanced stages (FIGO stages II-IV), a nine-fold HR for DSS and overall survival (OS) compared with POLE wild-type was identified. After controlling for treatment effects using Cox proportional HR, advanced-stage POLE-mutated tumors had a significantly higher HR of 8.67 for DSS compared with POLE-wild-type tumors of the same stage.
Conclusion: This study identified a unique set of POLE mutations in Indian EC patients associated with poor prognosis, which were particularly pronounced in advanced stages. Advanced stage of presentation, type of POLE mutations, and possibly ethnicity are predictors of adverse outcomes in POLE-mutated EC. The present study highlights ethnicity as a determinant of phenotypic expression of genetic change.
(© 2024 International Federation of Gynecology and Obstetrics.)
Databáze: MEDLINE
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