Evidence map›Paper›PMID 42690860›Full record

ArticleThe Indian journal of medical research2026

Molecular subtyping and POLE mutation spectrum in endometrial carcinoma.

Megha Uppin, Derin Mary Thomas, Rajshekhar Shantappa, Meher Lakshmi Konatam, Ranganath Ratnagiri, Kaushik Puranum, Khalid Razzak, Shantveer G Uppin

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Article in The Indian journal of medical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

8 authors.

Megha UppinDepartment of Pathology, Nizams Institute of Medical Sciences, Hyderabad, Telangana, India.
Derin Mary ThomasDepartment of Pathology, Nizams Institute of Medical Sciences, Hyderabad, Telangana, India.
Rajshekhar ShantappaDepartment of Surgical Oncology, Nizams Institute of Medical Sciences, Hyderabad, Telangana, India.
Meher Lakshmi KonatamDepartment of Medical Oncology, Nizams Institute of Medical Sciences, Hyderabad, Telangana, India.
Ranganath RatnagiriDepartment of Surgical Oncology, Nizams Institute of Medical Sciences, Hyderabad, Telangana, India.
Kaushik PuranumDepartment of Multi Disciplinary Research Unit, Nizams Institute of Medical Sciences, Hyderabad, Telangana, India.
Khalid RazzakDepartment of Pathology, Nizams Institute of Medical Sciences, Hyderabad, Telangana, India.
Shantveer G UppinDepartment of Pathology, Nizams Institute of Medical Sciences, Hyderabad, Telangana, India.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background and objectives Endometrial carcinoma is the most common gynaecological malignancy and an emerging global health concern with limited molecular data from Indian cohorts. Our study investigated the molecular subtypes and POLE gene mutation spectrum in the South Indian cohort. Methods Molecular subtyping was carried out using ProMisE classification, categorising patients into four molecular subgroups. This involved immunohistochemistry for mismatch repair proteins, p53abn, and Sanger sequencing for POLE mutations. POLE variants were further classified, and the pathogenicity was evaluated using in silico tools. Results Histopathology presented endometrioid carcinoma in 84.9% (n= 45) cases in our study. Molecular classification revealed POLE ultra-mutated (3.8%, n=2), MMR-deficient (18.9%, n=10), p53-abnormal (17.0%, n=9), and NSMP (37.7%, n=20) subgroups. POLE gene sequencing identified 11 exonuclease domain variants, including the recurrent endometrial carcinoma hotspot V411L (3.8% ,n=2) and ten non-hotspot variants such as T323I, T457M, T466I, V460M, L306P, P441S, A465V, T290I, E321K, and T278A (22.6%, n=12). Among these, six variants T466I, V460M, L306P, P441S, T290I, and E321K were unique in our cohort, and V460M, P441S, T290I, and E321K were predicted to have oncogenic potential. Clinically, p53abn tumours showed an aggressive phenotype with higher rates of advanced-stage disease and chemotherapy use (55.6%, n=5) compared with POLE-mutated (n=0), Mismatch repair-deficient (MMRd) (37.5%, n=3), and no specific molecular profile (NSMP) tumours (10.0%, n=2). Interpretation and conclusions This study demonstrates that integrating molecular profiling with histopathology to develop clinically applicable assays strengthens endometrial carcinoma classification and improves routine prognostic assessment.

Indexed as

DNA Polymerase IIEndometrial NeoplasmsPoly-ADP-Ribose Binding ProteinsAdultAgedDNA Mismatch RepairFemaleHumansIndiaMiddle AgedMutationTumor Suppressor Protein p53DNA Polymerase IIPOLE protein, humanPoly-ADP-Ribose Binding ProteinsTumor Suppressor Protein p53Endometrial carcinomaGynaecological malignancyIn-silico analysisPathogenic mutationsPole exonuclease domain mutationsVariants

Identifiers

PMID42690860
PMCPMC13541202

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