{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:15:17Z","timestamp":1788257717607,"version":"build-2803163510"},"reference-count":30,"publisher":"Scientific Scholar","content-domain":{"domain":["ijmr.org.in"],"crossmark-restriction":true},"short-container-title":["Indian J Med Res"],"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>POLE<\/jats:italic>\n                      gene mutation spectrum in the South Indian cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>POLE<\/jats:italic>\n                      mutations.\n                      <jats:italic>POLE<\/jats:italic>\n                      variants were further classified, and the pathogenicity was evaluated using\n                      <jats:italic>in silico<\/jats:italic>\n                      tools.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Histopathology presented endometrioid carcinoma in 84.9% (n= 45) cases in our study. Molecular classification revealed\n                      <jats:italic>POLE<\/jats:italic>\n                      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.\n                      <jats:italic>POLE<\/jats:italic>\n                      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\n                      <jats:italic>POLE<\/jats:italic>\n                      -mutated (n=0), Mismatch repair-deficient (MMRd) (37.5%, n=3), and no specific molecular profile (NSMP) tumours (10.0%, n=2).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation and conclusions<\/jats:title>\n                    <jats:p>This study demonstrates that integrating molecular profiling with histopathology to develop clinically applicable assays strengthens endometrial carcinoma classification and improves routine prognostic assessment.<\/jats:p>\n                  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