Abstract 3339: Evaluation of GATA6 and KRT17 immunostaining for subtype classification in pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with poor survival outcomes. Transcriptomic profiling has identified distinct PDAC subtypes associated with survival, highlighting their clinical relevance. However, reliance on RNA sequencing for subtype classification is not feasible in routine clinical practice, underscoring the need for surrogate biomarkers that are both effective and practical for predicting patient outcomes. This study evaluated GATA6 and KRT17 as multiplex immunohistochemistry (IHC) biomarkers to develop a prognostic model for PDAC subtype classification. Using a tissue microarray (TMA) comprising 130 patient-derived xenografts (PDXs), we quantified cell IHC positivity and stratified samples into subtypes based on GATA6 and KRT17 expression. Whole-slide staining of representative patient tumors validated the consistency of subtype classifications between PDXs and corresponding patient tumors. Patient TMAs (224 cores from 82 tumors) were subsequently analyzed to refine the classification system, incorporating GATA6 and KRT17 positive cell percentages, staining intensity (H-scores), and clinical variables into a comprehensive prognostic model. Initial classification based on PDX models demonstrated non-significant distinct survival trends (p=0.14), likely due to sample size limitations. However, a refined model applied to patient TMAs that incorporated additional parameters effectively stratified patients into prognostic groups with significantly different overall survival (p=0.042). These findings highlight the utility of GATA6 and KRT17 as surrogate classifiers for PDAC subtype classification and prognostication, offering a practical alternative to transcriptomic sequencing in HR-proficient PDAC. Citation Format: Ruomeng Fang, Joan Miguel Romero, Yifan Wang, Alicia Gomez Mendez, Adeline Cuggia, George Zogopoulos. Evaluation of GATA6 and KRT17 immunostaining for subtype classification in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3339.