Original articles

Vol. 118: Issue 4 - August 2026

Diagnostic Concordance Assessment for gene fusion identification: a multi-institutional experience

Authors

Simonetta Buglioni , Francesco Coletta , Piero Luigi Alò , Daniela Bastianelli , Concetta Cafiero , Raffaella Carletti , Tonia Cenci , Caterina Chiappetta , Giulia d'Amati , Maria De Bonis , Elena De Falco , Anna Di Benedetto , Claudio Di Cristofano , Amedeo Ferlosio , Dino Galafate , Alvaro Leone , Martina Lipari , Maria Cristina Macciomei , Angelo Minucci , Federica Natoni , Gloria Pessina , Daniela Righi , Marco Rosati , Umberto Malapelle , Giuseppe Perrone , Stefania Scarpino

Keywords: NSCLC, molecular diagnostics, gene fusions, MET exon 14 skipping, molecular reporting
DOI: 10.32074/1591-951X-2026
Publication Date: 2026-11-09

Summary

Background. Molecular profiling is essential for the therapeutic management of advanced NSCLC; however, the detection of gene fusions involving ALK, ROS1, RET and NTRK, as well as MET exon 14 skipping events, is technically and interpretatively more challenging than routine sequence variant testing. Heterogeneous diagnostic workflows across laboratories may affect result comparability and reporting consistency. This study aimed to evaluate inter-laboratory concordance for these alterations and to develop a harmonized molecular reporting format within the Lazio Region.

Materials and Methods. Eleven molecular pathology laboratories analyzed nine FFPE NSCLC samples, previously selected and validated by three coordinating institutions. Samples were processed according to local workflows using RT-qPCR and/or NGS, with IHC or FISH when applicable. Inter-laboratory concordance and reporting practices were assessed.

Results. Overall, 81.8% of laboratories correctly identified all expected alterations. Two Institutions each missed a single gene fusion event, mainly due to poor RNA quality or prolonged FFPE storage. Challenges were observed in NTRK1 fusion detection and in samples showing 3′/5′ imbalance. Marked heterogeneity in molecular reporting prompted the development and unanimous adoption of a unified regional template.

Conclusions. High diagnostic concordance was achieved despite methodological heterogeneity. Standardized molecular reporting represents a key step toward harmonizing predictive diagnostics and ensuring equitable access to precision oncology across the regional network.

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Authors

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

Francesco Coletta - Pathology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy

Piero Luigi Alò - UOC Anatomic Pathology Unit, Fabrizio Spaziani Hospital, Frosinone, Italy

Daniela Bastianelli - Unit of Molecular Pathology, University Department of Pathological Anatomy, ICOT Hospital, Latina, Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Italy

Concetta Cafiero - UOC Anatomic Pathology Unit, Fabrizio Spaziani Hospital, Frosinone, Italy

Raffaella Carletti - Department of Pathology, AOU Policlinico Umberto I, Sapienza University of Rome, Italy

Tonia Cenci - Department of Biomedicine and Prevention, Sections of Anatomy and Pathological Histology and Human Anatomy, Tor Vergata University of Rome, Rome, Italy

Caterina Chiappetta - Department of Pathology, AOU Policlinico Umberto I, Sapienza University of Rome, Italy

Giulia d'Amati - Dept of Radiological, Oncological and Pathological Sciences Sapienza, University of Rome, Policlinico Umberto I, Italy

Maria De Bonis - Departmental Unit of Molecular and Genomic Diagnostics, Genomics Core Facility, G-STeP, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy

Elena De Falco - Unit of Clinical Pathology, ICOT Hospital, Latina, Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Italy

Anna Di Benedetto - Pathology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy

Claudio Di Cristofano - Unit of Molecular Pathology, University Department of Pathological Anatomy, ICOT Hospital, Latina, Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Italy

Amedeo Ferlosio - Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy

Dino Galafate - Morphologic and Molecular Pathology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, Italy

Alvaro Leone - UOC Anatomic Pathology Unit, San Camillo-Forlanini Hospitals, Rome, Italy

Martina Lipari - UOC Anatomic Pathology, Sandro Pertini Hospitals ASL ROMA 2 Rome, Italy

Maria Cristina Macciomei - UOC Anatomic Pathology Unit, San Camillo-Forlanini Hospitals, Rome, Italy

Angelo Minucci - Departmental Unit of Molecular and Genomic Diagnostics, Genomics Core Facility, G-STeP, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy

Federica Natoni - UOSD Medical Genetics Laboratory at Santa Rosa Hospital ASL Viterbo, Italy

Gloria Pessina - UOSD Medical Genetics Laboratory at Santa Rosa Hospital ASL Viterbo, Italy

Daniela Righi - Anatomical Pathology Operative Research Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy

Marco Rosati - UOC Anatomic Pathology, Sandro Pertini Hospitals ASL ROMA 2 Rome, Italy

Umberto Malapelle - Department of Public Health, University of Naples Federico II, Naples, Italy

Giuseppe Perrone - Anatomical Pathology Operative Research Unit, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy. Research Unit of Anatomical Pathology, Department of Medicine and Surgery, Università Campus Bio-Medico Di Roma, Rome, Italy

Stefania Scarpino - Morphologic and Molecular Pathology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, 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
Buglioni, S., Coletta, F., Alò, P. L., Bastianelli, D., Cafiero, C., Carletti, R., Cenci, T., Chiappetta, C., d’Amati, G., De Bonis, M., De Falco, E., Di Benedetto, A., Di Cristofano, C., Ferlosio, A., Galafate, D., Leone, A., Lipari, M., Macciomei, M. C., Minucci, A., Natoni, F., Pessina, G., Righi, D., Rosati, M., Malapelle, U., Perrone, G., & Scarpino, S. (2026). Diagnostic Concordance Assessment for gene fusion identification: a multi-institutional experience. Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology, 118(4). https://doi.org/10.32074/1591-951X-2026
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