Oncology and Therapy (Jan 2024)
Non-Small Cell Lung Cancer Testing on Reference Specimens: An Italian Multicenter Experience
- Francesco Pepe,
- Gianluca Russo,
- Alessandro Venuta,
- Claudia Scimone,
- Mariantonia Nacchio,
- Pasquale Pisapia,
- Gaia Goteri,
- Francesca Barbisan,
- Caterina Chiappetta,
- Angelina Pernazza,
- Domenico Campagna,
- Marco Giordano,
- Giuseppe Perrone,
- Giovanna Sabarese,
- Annalisa Altimari,
- Dario de Biase,
- Giovanni Tallini,
- Daniele Calistri,
- Elisa Chiadini,
- Laura Capelli,
- Alfredo Santinelli,
- Anna Elisa Gulini,
- Elisa Pierpaoli,
- Manuela Badiali,
- Stefania Murru,
- Riccardo Murgia,
- Elena Guerini Rocco,
- Konstantinos Venetis,
- Nicola Fusco,
- Denise Morotti,
- Andrea Gianatti,
- Daniela Furlan,
- Giulio Rossi,
- Laura Melocchi,
- Maria Russo,
- Caterina De Luca,
- Lucia Palumbo,
- Saverio Simonelli,
- Antonella Maffè,
- Paola Francia di Celle,
- Tiziana Venesio,
- Maria Scatolini,
- Enrico Grosso,
- Sara Orecchia,
- Matteo Fassan,
- Mariangela Balistreri,
- Elisabetta Zulato,
- Daniela Reghellin,
- Elena Lazzari,
- Maria Santacatterina,
- Maria Liliana Piredda,
- Manuela Riccardi,
- Licia Laurino,
- Elena Roz,
- Domenico Longo,
- Daniela Petronilla Romeo,
- Carmine Fazzari,
- Andrea Moreno-Manuel,
- Giuseppe Diego Puglia,
- Andrey D. Prjibelski,
- Daria Shafranskaya,
- Luisella Righi,
- Angela Listì,
- Domenico Vitale,
- Antonino Iaccarino,
- Umberto Malapelle,
- Giancarlo Troncone
Affiliations
- Francesco Pepe
- Department of Public Health, Federico II University of Naples
- Gianluca Russo
- Department of Public Health, Federico II University of Naples
- Alessandro Venuta
- Department of Public Health, Federico II University of Naples
- Claudia Scimone
- Department of Public Health, Federico II University of Naples
- Mariantonia Nacchio
- Department of Public Health, Federico II University of Naples
- Pasquale Pisapia
- Department of Public Health, Federico II University of Naples
- Gaia Goteri
- Pathological Anatomy Institute, Polytechnic University of Marche Region
- Francesca Barbisan
- Pathological Anatomy Institute, Polytechnic University of Marche Region
- Caterina Chiappetta
- Department of Pathology, AOU Policlinico Umberto I
- Angelina Pernazza
- Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino-Sapienza University
- Domenico Campagna
- Department of Pathology, San Giovanni-Addolorata Hospital
- Marco Giordano
- Department of Pathology, San Giovanni-Addolorata Hospital
- Giuseppe Perrone
- Research Unit of Anatomical Pathology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma
- Giovanna Sabarese
- Anatomical Pathology Operative Research Unit, Fondazione Policlinico Universitario Campus Bio-Medico
- Annalisa Altimari
- Molecular Pathology, University of Bologna Hospital of Bologna Sant’Orsola-Malpighi Polyclinic
- Dario de Biase
- Pharmacy and Biotechnology (FaBiT), Molecular Pathology Laboratory, University of Bologna
- Giovanni Tallini
- Molecular Pathology, University of Bologna Hospital of Bologna Sant’Orsola-Malpighi Polyclinic
- Daniele Calistri
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”
- Elisa Chiadini
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”
- Laura Capelli
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”
- Alfredo Santinelli
- Anatomic Pathology Azienda Sanitaria Territoriale Pesaro-Urbino
- Anna Elisa Gulini
- Anatomic Pathology Azienda Sanitaria Territoriale Pesaro-Urbino
- Elisa Pierpaoli
- Anatomic Pathology Azienda Sanitaria Territoriale Pesaro-Urbino
- Manuela Badiali
- Laboratory of Genetics and Genomics-Pediatric Hospital A.Cao-ASL8
- Stefania Murru
- Laboratory of Genetics and Genomics-Pediatric Hospital A.Cao-ASL8
- Riccardo Murgia
- Experimental Medicine Unit, Department of Biomedical Sciences, University of Cagliari
- Elena Guerini Rocco
- Division of Pathology, IEO, European Institute of Oncology IRCCS
- Konstantinos Venetis
- Division of Pathology, IEO, European Institute of Oncology IRCCS
- Nicola Fusco
- Division of Pathology, IEO, European Institute of Oncology IRCCS
- Denise Morotti
- Pathology Unit and Medical Genetics Laboratory, Papa Giovanni XXIII Hospital
- Andrea Gianatti
- Pathology Unit and Medical Genetics Laboratory, Papa Giovanni XXIII Hospital
- Daniela Furlan
- Pathology Unit, Department of Medicine and Technological Innovation, University of Insubria
- Giulio Rossi
- Department of Anatomical Pathology, Fondazione Poliambulanza
- Laura Melocchi
- Department of Anatomical Pathology, Fondazione Poliambulanza
- Maria Russo
- Department of Public Health, Federico II University of Naples
- Caterina De Luca
- Department of Public Health, Federico II University of Naples
- Lucia Palumbo
- Department of Public Health, Federico II University of Naples
- Saverio Simonelli
- Department of Public Health, Federico II University of Naples
- Antonella Maffè
- Genetics and Molecular Biology Unit, Santa Croce e Carle Hospital
- Paola Francia di Celle
- Molecular Pathology, AOU Città della Salute e della Scienza di Torino
- Tiziana Venesio
- Candiolo Cancer Institute, FPO-IRCCS
- Maria Scatolini
- Molecular Oncology Lab, Fondazione Edo ed Elvo Tempia
- Enrico Grosso
- Molecular Oncology Lab, Fondazione Edo ed Elvo Tempia
- Sara Orecchia
- Pathology Division, S. Antonio and Biagio Hospital
- Matteo Fassan
- Department of Medicine-DIMED, University of Padua
- Mariangela Balistreri
- Surgical Pathology Unit, University Hospital of Padua
- Elisabetta Zulato
- Surgical Pathology Unit, University Hospital of Padua
- Daniela Reghellin
- Department of Pathology, San Bortolo Hospital
- Elena Lazzari
- Department of Pathology, San Bortolo Hospital
- Maria Santacatterina
- Department of Pathology, San Bortolo Hospital
- Maria Liliana Piredda
- Department of Pathology, San Bortolo Hospital
- Manuela Riccardi
- Department of Pathology, Azienda Ulss3 Serenissima, Ospedale dell’Angelo
- Licia Laurino
- Department of Pathology, Azienda Ulss3 Serenissima, Ospedale dell’Angelo
- Elena Roz
- Pathology Unit, La Maddalena Clinic for Cancer
- Domenico Longo
- UOSD di Anatomia Patologica dell’Azienda Ospedaliera Papardo
- Daniela Petronilla Romeo
- UOSD di Anatomia Patologica dell’Azienda Ospedaliera Papardo
- Carmine Fazzari
- UOSD di Anatomia Patologica dell’Azienda Ospedaliera Papardo
- Andrea Moreno-Manuel
- Molecular Oncology Laboratory, Fundación Investigación Hospital General Universitario de Valencia
- Giuseppe Diego Puglia
- Institute for Agricultural and Forest Systems in the Mediterranean, National Research Council (ISAFOM-CNR)
- Andrey D. Prjibelski
- Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, St. Petersburg State University
- Daria Shafranskaya
- Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, St. Petersburg State University
- Luisella Righi
- Department of Oncology, San Luigi Hospital, University of Turin
- Angela Listì
- Department of Oncology, San Luigi Hospital, University of Turin
- Domenico Vitale
- Department of Public Health, Federico II University of Naples
- Antonino Iaccarino
- Department of Public Health, Federico II University of Naples
- Umberto Malapelle
- Department of Public Health, Federico II University of Naples
- Giancarlo Troncone
- Department of Public Health, Federico II University of Naples
- DOI
- https://doi.org/10.1007/s40487-023-00252-5
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 73 – 95
Abstract
Abstract Introduction Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples. Methods Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon 19 EGFR (epidermal growth factor receptor) p.E746_AT50del, exon 2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene 1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon 14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico II before shipment. Methodological and molecular data from reference specimens were annotated. Results Overall, a median DNA concentration of 3.3 ng/µL (range 0.1–10.0 ng/µL) and 13.4 ng/µL (range 2.0–45.8 ng/µL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7 ng/µL (range 0.2–11.9 ng/µL) and 9.3 ng/µL (range 0.5–18.0 ng/µL) were also detected. KRAS exon 2 p.G12C, EGFR exon 19 p.E736_A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon 14 skipping mutation. Conclusions Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice.
Keywords
