Validation of a Novel Three-Dimensional (3D Fusion) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 Study

Journal of Personalized Medicine

Filippo Alongi¹  Maurizio Scaltriti²  Pasquale Rescigno³  Giuseppe Luigi Banna³  Camillo Porta⁴  Roberto Perris⁵  Alessio Signori⁶  Andrea Cossarizza⁷  Luisa Barzon⁸  Giulia Masi⁸  Brett Delahunt⁹  Holger Moch^1,10  Yoseba Aberasturi Plata^1,11  Piergiuseppe Colombo^1,12  Enrico Bollito^1,13  Matteo Fassan^1,14  Marta Sbaraglia^1,14  Angelo Paolo Dei Tos^1,14  Francesca Galuppini^1,14  Maurizio Colecchia^1,15  Roberto Bortolus^1,16  Giorgio Malpeli^1,17  Stefano Gobbo^1,18  Roberto Salvioni^1,19  Marcello Tucci^2,20  Roberto Sabbatini^2,21  Martina Fanelli^2,21  Maddalena Donini^2,22  Bruno Perrucci^2,22  Stefano Panni^2,22  Maria Olga Giganti^2,22  Rodolfo Passalacqua^2,22  Giuseppe Procopio^2,23  Elena Verzoni^2,23  Veronica Prati^2,24  Cinzia Ortega^2,24  Giuseppe Fornarini^2,25  Sara Elena Rebuzzi^2,25  Sergio Bracarda^2,26  Sebastiano Buti^2,27  Melissa Bersanelli^2,27  Michele Milella^2,28  Francesco Pierconti^2,29  Mimma Rizzo^3,30  Alessandro Antonelli^3,31  Alessandro Tafuri^3,31  Maria Angela Cerruto^3,31  Alessandro Volpe^3,32  Giario Conti^3,33  Alberto Lapini^3,34  Ilaria Montagnani^3,35  Paolo Umari^3,35  Maria Rosaria Raspollini^3,35  Giovanni Pappagallo^3,36  Miguel Angel Llaja Obispo^3,37  Francesco Massari^3,38  Umberto Basso^3,39  Marco Maruzzo^3,39  Francesco Atzori^4,40  Alessandra Mosca^4,41  Mattia Barbareschi^4,42  Luca Cima^4,42  Carlo Patriarca^4,43  Manuela Villanova^4,44  Anna Caliò^4,44  Serena Ammendola^4,44  Guido Martignoni^4,44  Albino Eccher^4,44  Matteo Brunelli^4,44  Federica Zito-Marino^4,45  Renato Franco^4,45  Enrico Munari^4,46  Valerio Gaetano Vellone^4,47  Gabriele Gaggero^4,47  Roberto Iacovelli^4,48  Gianluca Giannarini^4,49 

[1] Advanced Radiation Oncology Department, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, 37024 Verona, Italy;AstraZeneca, New York, NY 10005, USA;Candiolo Cancer Institute, FPO-IRCCS, Candiolo, 10060 Turin, Italy;Department of Biomedical Sciences and Human Oncology, University of Bari ‘A. Moro’, 70121 Bari, Italy;Department of Biosciences, COMT-Centre for Molecular and Translational Oncology, University of Parma, 43124 Parma, Italy;Department of Health Sciences (DISSAL), Section of Biostatistics, University of Genova, 16100 Genova, Italy;Department of Medical and Surgical Sciences for Children and Adults, University of Modena & Reggio Emilia, 41121 Modena, Italy;Department of Molecular Medicine, University of Padua, 35100 Padova, Italy;Department of Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, University of Otago, 3743 Wellington, New Zealand;Department of Pathology and Molecular Pathology, University Hospital Zurich, 8006 Zurich, Switzerland;Department of Pathology, Cruces University Hospital, University of the Basque Country (UPV/EHU), 48900 Barakaldo, Spain;Department of Pathology, Department of Biomedical Sciences, Humanitas University, IRCCS Humanitas Clinical and Research Hospital, Pieve Emanuele, 20089 Milan, Italy;Department of Pathology, San Luigi Gonzaga Hospital, University of Turin, 10122 Torino, Italy;Department of Pathology, University and Hospital Trust of Padua, 35128 Padova, Italy;Department of Pathology, Uropathology Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele, 20132 Milano, Italy;Department of Radiotherapy, CRO, 33081 Aviano, Italy;Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37134 Verona, Italy;Department of Translation Medicine, Pathology Unit, University of Ferrara, 44100 Ferrara, Italy;Department of Urology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy;Division of Oncology, Cardinal Massaia Hospital, 14100 Asti, Italy;Division of Oncology, Department of Oncology, Hematology & Respiratory Diseases, University of Modena & Reggio Emilia, 41121 Modena, Italy;Division of Oncology, Hospital Trust of Cremona, 26100 Cremona, Italy;Division of Oncology, IRCCS Foundation, Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy;Division of Oncology, Institute for Cancer Research and Treatment, Asl Cn2 Alba-Brà, 12042 Cuneo, Italy;Division of Oncology, San Martino Hospital, 16100 Genova, Italy;Division of Oncology, Santa Maria Hospital, 05100 Terni, Italy;Division of Oncology, University and Hospital Trust of Parma, 43100 Parma, Italy;Division of Oncology, University and Hospital Trust of Verona, 37134 Verona, Italy;Division of Pathology, Policlinico Universitario Fondazione Agostino Gemelli, 00168 Roma, Italy;Division of Translational Oncology, IRCCS Istituti Clinici Scientifici ‘Maugeri’, 27100 Pavia, Italy;Division of Urology, Department of Surgery, Dentistry, Paediatrics and Gynaecology, University and Hospital Trust of Verona, 37134 Verona, Italy;Division of Urology, Maggiore della Carità Hospital, 28100 Novara, Italy;Division of Urology, Sant’Anna Hospital, 22100 Como, Italy;Division of Urology, University Hospital Careggi, 50100 Firenze, Italy;Histopathology and Molecular Diagnostics, University Hospital Careggi, 50100 Firenze, Italy;Indipendent Researcher, Clinical Epidemiologist, Silea, 31057 Treviso, Italy;Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16100 Genova, Italy;Medical Oncology, University and Hospital Trust of Bologna, 40138 Bologna, Italy;Oncology Unit, Oncology Department, Istituto Oncologico Veneto (IOV), IRCCS, 35128 Padua, Italy;Oncology Unit, University and Hospital Trust of Cagliari, 09100 Cagliari, Italy;Oncology, Candiolo Cancer Institute, IRCCS-FPO, 10060 Torino, Italy;Pathology Unit, Department of Clinical Services, Santa Chiara Hospital, 38100 Trento, Italy;Pathology Unit, Department of Clinical Services, Sant’Anna Hospital, 22100 Como, Italy;Pathology Unit, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, 37134 Verona, Italy;Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania ‘Luigi Vanvitelli’, 81100 Caserta, Italy;Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, 25100 Brescia, Italy;Pathology Unit, San Martino Hospital, 16100 Genova, Italy;Policlinico Universitario Fondazione Andrea Gemelli, 00168 Roma, Italy;Urology Unit, “Santa Maria della Misericordia”, University of Udine, 33100 Udine, Italy;

关键词: clear cell renal cell carcinoma;    tumor sampling;    intratumoral heterogeneity;    angiogenesis;    immunity;    immunohistochemistry;   

DOI  :  10.3390/jpm12050727

来源: DOAJ

【 摘 要 】

We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3–G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion (p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes (p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods (p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.

【 授权许可】

Unknown