Mutation profile and therapeutic implications in Peutz-Jeghers syndrome-associated gastric-type endocervical...

Gastric-type endocervical adenocarcinoma (G-EAC) is a rare, highly aggressive malignancy that is not associated with human papillomavirus (HPV) infection. Its occurrence in patients with Peutz-Jeghers syndrome (PJS) is exceptionally rare but clinically critical. In this preliminary study, we performed comprehensive genomic profiling (CGP) using a targeted next-generation sequencing (NGS) panel and immunohistochemistry (IHC) for key biomarkers on a single, well-characterized patient with stage IB3 PJS-associated G-EAC. The primary objective was to identify actionable genomic alterations and potential therapeutic targets to inform personalized treatment strategies. CGP revealed a pathogenic germline STK11 p.K84* mutation, alongside somatic KRAS p.G12A and ERBB3 p.R667S mutations. IHC demonstrated strong, diffuse positivity for Claudin18.2 and MUC6, confirming a gastric phenotype, while p16 was negative. The integration of genomic and proteomic data revealed a primary actionable target, Claudin18.2 (a proven target in gastric cancer), alongside potential actionable alterations involving ERBB signaling. This proof-of-concept study may suggest that integrating CGP and IHC in the management of PJS-associated G-EAC is feasible and could potentially inform clinical decision-making. The identification of these targets could suggest a rationale for incorporating molecular profiling into the standard diagnostic workflow for this aggressive malignancy, potentially improving outcomes through precision oncology approaches.