Original articles

Vol. 117: Issue 5 - October 2025

MTAP in small biopsy samples of pancreatic lesions: a potential diagnostic biomarker. Immunohistochemical, fluorescence in situ hybridization and molecular analysis

Authors

Stefano Lucà , Cecilia Salzillo , Valeria Masola , Ferdinando De Vita , Danilo Porpora , Giovanni Conzo , Giovanni Savarese , Roberto Sirica , Immacolata Cozzolino , Eduardo Clery , Federica Zito Marino , Renato Franco , Marco Montella

Key words: pancreatic ductal adenocarcinoma, fine needle aspiration biopsies, immunohistochemistry, MTAP, CDKN2A
DOI: 10.32074/1591-951X-1243
Publication Date: 2025-12-16

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.

Downloads

PDF
Authors

Stefano Lucà - Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania "Luigi Vanvitelli", 80138 Naples, Italy

Cecilia Salzillo - Department of Precision and Regenerative Medicine and Ionian Area, Pathology Unit, University of Bari "Aldo Moro", 70121 Bari, Italy

Valeria Masola - Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania "Luigi Vanvitelli", 80138 Naples, Italy

Ferdinando De Vita - Department of Precision Medicine, Università Degli Studi Della Campania "Luigi Vanvitelli," Napoli, Italy

Danilo Porpora - Department of Translational Medical Sciences, University of Campania L. Vanvitelli, Napoli 80138, Campania, Italy

Giovanni Conzo - Department of Cardiothoracic Sciences, University of Campania "Luigi Vanvitelli", Division of General and Oncologic Surgery, Via Pansini 5, 80131 Napoli, Italy

Giovanni Savarese - AMES-Centro Polidiagnostico Strumentale, SRL, Naples, Italy

Roberto Sirica - AMES-Centro Polidiagnostico Strumentale, SRL, Naples, Italy

Immacolata Cozzolino - Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania "Luigi Vanvitelli", 80138 Naples, Italy

Eduardo Clery - Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania "Luigi Vanvitelli", 80138 Naples, Italy

Federica Zito Marino - Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania "Luigi Vanvitelli", 80138 Naples, Italy

Renato Franco - Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania "Luigi Vanvitelli", 80138 Naples, Italy

Marco Montella - Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania "Luigi Vanvitelli", 80138 Naples, Italy

License

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Copyright

Copyright (c) 2025 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology

How to Cite
Lucà, S., Salzillo, C., Masola, V., De Vita, F., Porpora, D., Conzo, G., Savarese, G., Sirica, R., Cozzolino, I., Clery, E., Zito Marino, F., Franco, R., & Montella, M. (2025). MTAP in small biopsy samples of pancreatic lesions: a potential diagnostic biomarker. Immunohistochemical, fluorescence in situ hybridization and molecular analysis. Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology, 117(5). https://doi.org/10.32074/1591-951X-1243
  • Abstract viewed - 9 times
  • PDF downloaded - 0 times