Molecular Characterization of Endometrial Cancer Using a Laboratory-Developed Multi-Gene NGS Panel

Résumé fourni par la source

Endometrial carcinoma is a biologically and clinically heterogeneous neoplasm, for which molecular classification now plays a central role in determining prognosis and guiding treatment. The aim of this study was to develop and apply an in-house multi-gene NGS panel to expand the molecular characterization of endometrial tumors beyond the markers required for surrogate classification. Seventy primary endometrial carcinomas were selected and analyzed by immunohistochemistry for p53, mismatch repair proteins, ARID1A, and PTEN, and by NGS on DNA extracted from FFPE samples using a panel comprising 28 genes. Molecular classification was assigned according to the WHO algorithm into the subgroups POLE-mutated, MMR-deficient, p53-abnormal, and NSMP (No Specific Molecular Profile). Sixty-eight cases were evaluable by sequencing, and in 93% at least one pathogenic, likely pathogenic, or variant of uncertain significance was identified. The most frequent alterations involved PTEN, PIK3CA, ARID1A, and TP53. POLE-mutated tumors showed the highest mutational burden, while CTNNB1 alterations were predominantly associated with the NSMP subgroup. Overall, the proposed panel proved to be a useful tool for complementing conventional molecular classification and for highlighting additional genomic differences that may be biologically and clinically relevant.

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