ArticlePathologica2025
MTAP in small biopsy samples of pancreatic lesions: a potential diagnostic biomarker. Immunohistochemical, fluorescence in situ hybridization and molecular analysis.
Article in Pathologica, 2025. 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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Abstract
Background: Most pancreatic ductal adenocarcinoma (PDAC) are diagnosed with fine needle aspiration biopsies (FNAB). Some benign mimickers exist, and the differential diagnosis can be challenging. Immunohistochemistry (IHC) is a useful diagnostic tool, and some biomarkers have been studied in this clinical setting. Homozygous deletion (HD) of CDKN2A is observed in about 40% of PDAC, and methylthioadenosine phosphorylase (MTAP) IHC has been identified as a reliable surrogate marker for this alteration. The aim of our study is to evaluate the value of MTAP IHC status in the diagnosis of PDAC. Materials and methods: We collected 27 EUS-FNAB of pancreatic masses. MTAP and S100P IHC were performed. The IHC status of MTAP has been correlated with CDKN2A molecular status studied by fluorescence in-situ hybridization (FISH) and next-generation sequencing (NGS). Results: Approximately 25% of FNAB diagnosed as PDAC showed complete loss of MTAP expression. Our results demonstrated a very high positive predictive value (100%), with a modest sensitivity (31.5%) but a high specificity (100%) for the diagnosis of PDAC. Regarding S100P, 71% of PDAC cases tested positive, whereas the only case diagnosed as benign was negative. The concordance between CDKN2A molecular status by FISH and MTAP expression by immunohistochemistry did not prove to be optimal. Interestingly, some FISH wild-type samples showed HD in NGS. Discussion: An immunohistochemical immunohistochemical panel including MTAP and S100P improves diagnostic accuracy in PDAC diagnosis, showing a better sensitivity (75%) and the same specificity compared to single markers. FISH showed an incomplete sensitivity in identifying all cases with HD of CDKN2A, with two cases MTAP negative by IHC and identified as deleted only by molecular study.
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