Original articles

Vol. 118: Issue 4 - August 2026

SIAPeC RARE-TARGET – VITA Project: A Large Nationwide Study on Immunophenotypic and Genomic Profiling of Rare Biomarkers in Solid Tumors: Cumulative and Preliminary Data

Authors

Antonio Marchetti , Caterina Marchiò , Mattia Barbareschi , Enrico Berrino , Emanuela Bonoldi , Fiamma Buttitta , Simonetta Buglioni , Michela Campora , Valentina Caputo , Francesco Giuseppe Carbone , Daniela Cesselli , Emanuela D'Angelo , Caterina De Luca , Anna Di Benedetto , Maurizio Di Bonito , Alessia Di Lorito , Gabriella Fontanini , Renato Franco , Alessandro Gambella , Paolo Graziano , Claudio Luchini , Luca Mastracci , Paola Mattiolo , Aldo Palange , Mauro Papotti , Emanuela Pilozzi , Giancarlo Pruneri , Andrea Ronchi , Daniela Russo , Stefania Scarpino , Giovanni Tallini , Giancarlo Troncone , Clara Ugolini , Emanuele Valtorta , Anna Sapino , Aldo Scarpa

Keywords: rare biomarkers, solid tumors, NGS, early-onset tumors, TMAs
DOI: 10.32074/1591-951X-2405
Publication Date: 2026-11-09

Summary

Background. Targeted therapies, based on the identification of actionable biomarkers, have revolutionized oncology. Agnostic strategies have further expanded treatment options by enabling targeted therapies irrespective of tumor site and histotype. However, the implementation of biomarker screening across diverse neoplasms, including rare tumors or tumors with rare mutations, is often limited by technical barriers. Against this background, the SIAPeC RARE-TARGET study aimed to evaluate the feasibility and clinical relevance of a low-cost, tissue microarray–based screening strategy for immunophenotypic and genomic profiling of rare targets within a nationwide project in Italy.

Methods.Tumor specimens from 9,826 patients, collected between 2015 and 2019 in 18 Italian centers, were processed and analyzed during 2020-2021. Samples included: 1) 1258 special-type tumors, 2) 1691 sarcomatous neoplasms, and 3) 6877 early-onset tumors (age ≤50 years). Tissue microarrays (TMAs) were constructed to enable high-throughput immunohistochemistry (IHC) screening for TRK, ALK, ROS1, BRAF V600E, and mismatch repair (MMR) proteins. Positive cases were validated using orthogonal next-generation sequencing (NGS) targeting gene mutations or fusions.

Results. Of the 9,826 tumors analyzed, 686 (7%) were found to be positive by IHC for at least one biomarker: TRK (1.9%), ALK (1.6%), ROS1 (0.8%), BRAF V600E (1.5%), and MMR deficiency (1.6%). The distribution of biomarker alterations differed significantly across the three major tumor groups analyzed. NGS analysis was feasible in 76% of screened-positive cases, with DNA quality issues accounting for the remainder. Significant inter-center variability in sequencing coverage and success rates highlighted technical challenges related to tissue preservation and pre-analytical conditions. 

Conclusion.The SIAPeC RARE-TARGET study demonstrates the feasibility and potential clinical utility of combining TMA-based IHC screening with NGS validation for the identification of rare biomarkers in a nationwide setting. The results underscore the importance of histology-agnostic testing approaches in diverse tumors and the urgent need for standardized pre-analytical protocols. Further detailed analyses of molecular data, along with comparative immunohistochemical evaluations across histotypes for the different biomarkers, will be presented in subsequent publications, providing insights to refine biomarker-driven strategies in pathology practice.

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Authors

Antonio Marchetti - Department of Medical Oral Biotechnological Sciences and CAST, Univeristy of Chieti, Integrated Pathology Unit, ASL2 Abruzzo, Chieti, Italy

Caterina Marchiò - Pathology Unit, FPO-IRCCS Candiolo Cancer Institute, Candiolo, Italy. Department of Medical Sciences, Univerity of Turin, Italy

Mattia Barbareschi - Pathology Unit, Azienda sanitaria universitaria integrata del Trentino, Italy

Enrico Berrino - Pathology Unit, FPO-IRCCS Candiolo Cancer Institute, Candiolo, Italy. Department of Medical Sciences, Univerity of Turin, Italy

Emanuela Bonoldi - Pathology Unit, Niguarda Cancer Center, Milan

Fiamma Buttitta - Department of Medical Oral Biotechnological Sciences and CAST, Univeristy of Chieti, Integrated Pathology Unit, ASL2 Abruzzo, Chieti, Italy

Simonetta Buglioni - Department of Pathology, IRCCS Regina Elena National Cancer Institute, Rome, Italy

Michela Campora - Pathology Unit, Azienda sanitaria universitaria integrata del Trentino, Italy

Valentina Caputo - Pathology Unit, Niguarda Cancer Center, Milan

Francesco Giuseppe Carbone - Pathology Unit, Azienda sanitaria universitaria integrata del Trentino, Italy

Daniela Cesselli - Department of Pathology, S. Maria della Misericordia University Hospital, Udine, Italy

Emanuela D'Angelo - Department of Medical Oral Biotechnological Sciences and CAST, Univeristy of Chieti, Integrated Pathology Unit, ASL2 Abruzzo, Chieti, Italy

Caterina De Luca - Department of Public Health, University of Naples Federico II, Naples, Italy

Anna Di Benedetto - Department of Pathology, IRCCS, Regina Elena Cancer Institute Rome, Italy

Maurizio Di Bonito - Pathology Unit, Istituto Nazionale Tumori, IRCCS, Fondazione G.Pascale, Naples, Italy

Alessia Di Lorito - Department of Medical Oral Biotechnological Sciences and CAST, Univeristy of Chieti, Integrated Pathology Unit, ASL2 Abruzzo, Chieti, Italy

Gabriella Fontanini - Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Italy

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

Alessandro Gambella - Pathology Unit, Department of Surgical Sciences and Integrated Diagnostic, University of Genoa, Italy; IRCCS AOM San Martino POliclinico Hospital of Genoa, Italy

Paolo Graziano - Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Italy

Claudio Luchini - ARC-Net Research Center and Department of Diagnostic and Public Health-Section of Pathology, Policlinico GB Rossi, Verona, Italy

Luca Mastracci - Pathology Unit, Department of Surgical Sciences and Integrated Diagnostic, University of Genoa, Italy; IRCCS AOM San Martino POliclinico Hospital of Genoa, Italy

Paola Mattiolo - ARC-Net Research Center and Department of Diagnostic and Public Health-Section of Pathology, Policlinico G.B. Rossi, Verona, Italy

Aldo Palange - Department of Pathology, IRCCS Regina Elena National Cancer Institute, Rome, Italy

Mauro Papotti - Department of Oncology, University of Turin, Italy

Emanuela Pilozzi - Morphologic and Molecular Pathology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, Italy

Giancarlo Pruneri - Department of Diagnostic Innovation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

Andrea Ronchi - Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli studi della Campania, "Luigi Vanvitelli", Naples, Italy

Daniela Russo - Department of Medical and Surgical Sciences, University of Naples Federico II, Naples, Italy

Stefania Scarpino - Morphologic and Molecular Pathology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea University Hospital, Sapzienza Univeristy of Rome, Italy

Giovanni Tallini - Department of Medical and Surgical Sciences (DIMEC) University of Bologna, Italy

Giancarlo Troncone - Department of Public Health, University of Naples, Federico II, Naples, Italy

Clara Ugolini - Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Italy

Emanuele Valtorta - Pathology Unit, Niguarda Cancer Center, Milan, Italy

Anna Sapino - Pathology Unit, FPO-IRCCS Candiolo Cancer Institute, Candiolo, Italy; Department of Medical Sciences, University of Turin, Italy

Aldo Scarpa - ARC-Net Research Center and Department of Diagnostic and Public Health-Section of Pathology, Policlinico G.B. Rossi, Verona, Italy

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Copyright

Copyright (c) 2026 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology

How to Cite
Marchetti, A., Marchiò, C., Barbareschi, M., Berrino, E., Bonoldi, E., Buttitta, F., Buglioni, S., Campora, M., Caputo, V., Carbone, F. G., Cesselli, D., D’Angelo, E. ., De Luca, C., Di Benedetto, A., Di Bonito, M., Di Lorito, A., Fontanini, G., Franco, R., Gambella, A., Graziano, P., Luchini, C., Mastracci, L., Mattiolo, P., Palange, A., Papotti, M., Pilozzi, E., Pruneri, G., Ronchi, A., Russo, D., Scarpino, S., Tallini, G., Troncone, G., Ugolini, C., Valtorta, E., Sapino, A., & Scarpa, A. (2026). SIAPeC RARE-TARGET – VITA Project: A Large Nationwide Study on Immunophenotypic and Genomic Profiling of Rare Biomarkers in Solid Tumors: Cumulative and Preliminary Data. Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology, 118(4). https://doi.org/10.32074/1591-951X-2405
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