Validation of a Novel Three-Dimensional (<i>3D Fusion</i>) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 Study
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/12/5/727 |
| _version_ | 1797498693512855552 |
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| author | Matteo Brunelli Guido Martignoni Giorgio Malpeli Alessandro Volpe Luca Cima Maria Rosaria Raspollini Mattia Barbareschi Alessandro Tafuri Giulia Masi Luisa Barzon Serena Ammendola Manuela Villanova Maria Angela Cerruto Michele Milella Sebastiano Buti Melissa Bersanelli Giuseppe Fornarini Sara Elena Rebuzzi Valerio Gaetano Vellone Gabriele Gaggero Giuseppe Procopio Elena Verzoni Sergio Bracarda Martina Fanelli Roberto Sabbatini Rodolfo Passalacqua Bruno Perrucci Maria Olga Giganti Maddalena Donini Stefano Panni Marcello Tucci Veronica Prati Cinzia Ortega Anna Caliò Albino Eccher Filippo Alongi Giovanni Pappagallo Roberto Iacovelli Alessandra Mosca Paolo Umari Ilaria Montagnani Stefano Gobbo Francesco Atzori Enrico Munari Marco Maruzzo Umberto Basso Francesco Pierconti Carlo Patriarca Piergiuseppe Colombo Alberto Lapini Giario Conti Roberto Salvioni Enrico Bollito Andrea Cossarizza Francesco Massari Mimma Rizzo Renato Franco Federica Zito-Marino Yoseba Aberasturi Plata Francesca Galuppini Marta Sbaraglia Matteo Fassan Angelo Paolo Dei Tos Maurizio Colecchia Holger Moch Maurizio Scaltriti Camillo Porta Brett Delahunt Gianluca Giannarini Roberto Bortolus Pasquale Rescigno Giuseppe Luigi Banna Alessio Signori Miguel Angel Llaja Obispo Roberto Perris Alessandro Antonelli |
| author_facet | Matteo Brunelli Guido Martignoni Giorgio Malpeli Alessandro Volpe Luca Cima Maria Rosaria Raspollini Mattia Barbareschi Alessandro Tafuri Giulia Masi Luisa Barzon Serena Ammendola Manuela Villanova Maria Angela Cerruto Michele Milella Sebastiano Buti Melissa Bersanelli Giuseppe Fornarini Sara Elena Rebuzzi Valerio Gaetano Vellone Gabriele Gaggero Giuseppe Procopio Elena Verzoni Sergio Bracarda Martina Fanelli Roberto Sabbatini Rodolfo Passalacqua Bruno Perrucci Maria Olga Giganti Maddalena Donini Stefano Panni Marcello Tucci Veronica Prati Cinzia Ortega Anna Caliò Albino Eccher Filippo Alongi Giovanni Pappagallo Roberto Iacovelli Alessandra Mosca Paolo Umari Ilaria Montagnani Stefano Gobbo Francesco Atzori Enrico Munari Marco Maruzzo Umberto Basso Francesco Pierconti Carlo Patriarca Piergiuseppe Colombo Alberto Lapini Giario Conti Roberto Salvioni Enrico Bollito Andrea Cossarizza Francesco Massari Mimma Rizzo Renato Franco Federica Zito-Marino Yoseba Aberasturi Plata Francesca Galuppini Marta Sbaraglia Matteo Fassan Angelo Paolo Dei Tos Maurizio Colecchia Holger Moch Maurizio Scaltriti Camillo Porta Brett Delahunt Gianluca Giannarini Roberto Bortolus Pasquale Rescigno Giuseppe Luigi Banna Alessio Signori Miguel Angel Llaja Obispo Roberto Perris Alessandro Antonelli |
| author_sort | Matteo Brunelli |
| collection | DOAJ |
| description | 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 (<i>p</i> = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes (<i>p</i> = 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 (<i>p</i> = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity. |
| first_indexed | 2024-03-10T03:36:59Z |
| format | Article |
| id | doaj.art-bce8f7fdb66b4c7983dcd6f042ec28a0 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T03:36:59Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-bce8f7fdb66b4c7983dcd6f042ec28a02023-11-23T11:43:49ZengMDPI AGJournal of Personalized Medicine2075-44262022-04-0112572710.3390/jpm12050727Validation of a Novel Three-Dimensional (<i>3D Fusion</i>) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 StudyMatteo Brunelli0Guido Martignoni1Giorgio Malpeli2Alessandro Volpe3Luca Cima4Maria Rosaria Raspollini5Mattia Barbareschi6Alessandro Tafuri7Giulia Masi8Luisa Barzon9Serena Ammendola10Manuela Villanova11Maria Angela Cerruto12Michele Milella13Sebastiano Buti14Melissa Bersanelli15Giuseppe Fornarini16Sara Elena Rebuzzi17Valerio Gaetano Vellone18Gabriele Gaggero19Giuseppe Procopio20Elena Verzoni21Sergio Bracarda22Martina Fanelli23Roberto Sabbatini24Rodolfo Passalacqua25Bruno Perrucci26Maria Olga Giganti27Maddalena Donini28Stefano Panni29Marcello Tucci30Veronica Prati31Cinzia Ortega32Anna Caliò33Albino Eccher34Filippo Alongi35Giovanni Pappagallo36Roberto Iacovelli37Alessandra Mosca38Paolo Umari39Ilaria Montagnani40Stefano Gobbo41Francesco Atzori42Enrico Munari43Marco Maruzzo44Umberto Basso45Francesco Pierconti46Carlo Patriarca47Piergiuseppe Colombo48Alberto Lapini49Giario Conti50Roberto Salvioni51Enrico Bollito52Andrea Cossarizza53Francesco Massari54Mimma Rizzo55Renato Franco56Federica Zito-Marino57Yoseba Aberasturi Plata58Francesca Galuppini59Marta Sbaraglia60Matteo Fassan61Angelo Paolo Dei Tos62Maurizio Colecchia63Holger Moch64Maurizio Scaltriti65Camillo Porta66Brett Delahunt67Gianluca Giannarini68Roberto Bortolus69Pasquale Rescigno70Giuseppe Luigi Banna71Alessio Signori72Miguel Angel Llaja Obispo73Roberto Perris74Alessandro Antonelli75Pathology Unit, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, 37134 Verona, ItalyPathology Unit, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, 37134 Verona, ItalyDepartment of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37134 Verona, ItalyDivision of Urology, Maggiore della Carità Hospital, 28100 Novara, ItalyPathology Unit, Department of Clinical Services, Santa Chiara Hospital, 38100 Trento, ItalyHistopathology and Molecular Diagnostics, University Hospital Careggi, 50100 Firenze, ItalyPathology Unit, Department of Clinical Services, Santa Chiara Hospital, 38100 Trento, ItalyDivision of Urology, Department of Surgery, Dentistry, Paediatrics and Gynaecology, University and Hospital Trust of Verona, 37134 Verona, ItalyDepartment of Molecular Medicine, University of Padua, 35100 Padova, ItalyDepartment of Molecular Medicine, University of Padua, 35100 Padova, ItalyPathology Unit, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, 37134 Verona, ItalyPathology Unit, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, 37134 Verona, ItalyDivision of Urology, Department of Surgery, Dentistry, Paediatrics and Gynaecology, University and Hospital Trust of Verona, 37134 Verona, ItalyDivision of Oncology, University and Hospital Trust of Verona, 37134 Verona, ItalyDivision of Oncology, University and Hospital Trust of Parma, 43100 Parma, ItalyDivision of Oncology, University and Hospital Trust of Parma, 43100 Parma, ItalyDivision of Oncology, San Martino Hospital, 16100 Genova, ItalyDivision of Oncology, San Martino Hospital, 16100 Genova, ItalyPathology Unit, San Martino Hospital, 16100 Genova, ItalyPathology Unit, San Martino Hospital, 16100 Genova, ItalyDivision of Oncology, IRCCS Foundation, Istituto Nazionale dei Tumori di Milano, 20133 Milano, ItalyDivision of Oncology, IRCCS Foundation, Istituto Nazionale dei Tumori di Milano, 20133 Milano, ItalyDivision of Oncology, Santa Maria Hospital, 05100 Terni, ItalyDivision of Oncology, Department of Oncology, Hematology & Respiratory Diseases, University of Modena & Reggio Emilia, 41121 Modena, ItalyDivision of Oncology, Department of Oncology, Hematology & Respiratory Diseases, University of Modena & Reggio Emilia, 41121 Modena, ItalyDivision of Oncology, Hospital Trust of Cremona, 26100 Cremona, ItalyDivision of Oncology, Hospital Trust of Cremona, 26100 Cremona, ItalyDivision of Oncology, Hospital Trust of Cremona, 26100 Cremona, ItalyDivision of Oncology, Hospital Trust of Cremona, 26100 Cremona, ItalyDivision of Oncology, Hospital Trust of Cremona, 26100 Cremona, ItalyDivision of Oncology, Cardinal Massaia Hospital, 14100 Asti, ItalyDivision of Oncology, Institute for Cancer Research and Treatment, Asl Cn2 Alba-Brà, 12042 Cuneo, ItalyDivision of Oncology, Institute for Cancer Research and Treatment, Asl Cn2 Alba-Brà, 12042 Cuneo, ItalyPathology Unit, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, 37134 Verona, ItalyPathology Unit, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, 37134 Verona, ItalyAdvanced Radiation Oncology Department, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, 37024 Verona, ItalyIndipendent Researcher, Clinical Epidemiologist, Silea, 31057 Treviso, ItalyPoliclinico Universitario Fondazione Andrea Gemelli, 00168 Roma, ItalyOncology, Candiolo Cancer Institute, IRCCS-FPO, 10060 Torino, ItalyHistopathology and Molecular Diagnostics, University Hospital Careggi, 50100 Firenze, ItalyHistopathology and Molecular Diagnostics, University Hospital Careggi, 50100 Firenze, ItalyDepartment of Translation Medicine, Pathology Unit, University of Ferrara, 44100 Ferrara, ItalyOncology Unit, University and Hospital Trust of Cagliari, 09100 Cagliari, ItalyPathology Unit, Department of Molecular and Translational Medicine, University of Brescia, 25100 Brescia, ItalyOncology Unit, Oncology Department, Istituto Oncologico Veneto (IOV), IRCCS, 35128 Padua, ItalyOncology Unit, Oncology Department, Istituto Oncologico Veneto (IOV), IRCCS, 35128 Padua, ItalyDivision of Pathology, Policlinico Universitario Fondazione Agostino Gemelli, 00168 Roma, ItalyPathology Unit, Department of Clinical Services, Sant’Anna Hospital, 22100 Como, ItalyDepartment of Pathology, Department of Biomedical Sciences, Humanitas University, IRCCS Humanitas Clinical and Research Hospital, Pieve Emanuele, 20089 Milan, ItalyDivision of Urology, University Hospital Careggi, 50100 Firenze, ItalyDivision of Urology, Sant’Anna Hospital, 22100 Como, ItalyDepartment of Urology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milano, ItalyDepartment of Pathology, San Luigi Gonzaga Hospital, University of Turin, 10122 Torino, ItalyDepartment of Medical and Surgical Sciences for Children and Adults, University of Modena & Reggio Emilia, 41121 Modena, ItalyMedical Oncology, University and Hospital Trust of Bologna, 40138 Bologna, ItalyDivision of Translational Oncology, IRCCS Istituti Clinici Scientifici ‘Maugeri’, 27100 Pavia, ItalyPathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania ‘Luigi Vanvitelli’, 81100 Caserta, ItalyPathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania ‘Luigi Vanvitelli’, 81100 Caserta, ItalyDepartment of Pathology, Cruces University Hospital, University of the Basque Country (UPV/EHU), 48900 Barakaldo, SpainDepartment of Pathology, University and Hospital Trust of Padua, 35128 Padova, ItalyDepartment of Pathology, University and Hospital Trust of Padua, 35128 Padova, ItalyDepartment of Pathology, University and Hospital Trust of Padua, 35128 Padova, ItalyDepartment of Pathology, University and Hospital Trust of Padua, 35128 Padova, ItalyDepartment of Pathology, Uropathology Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele, 20132 Milano, ItalyDepartment of Pathology and Molecular Pathology, University Hospital Zurich, 8006 Zurich, SwitzerlandAstraZeneca, New York, NY 10005, USADepartment of Biomedical Sciences and Human Oncology, University of Bari ‘A. Moro’, 70121 Bari, ItalyDepartment of Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, University of Otago, 3743 Wellington, New ZealandUrology Unit, “Santa Maria della Misericordia”, University of Udine, 33100 Udine, ItalyDepartment of Radiotherapy, CRO, 33081 Aviano, ItalyCandiolo Cancer Institute, FPO-IRCCS, Candiolo, 10060 Turin, ItalyCandiolo Cancer Institute, FPO-IRCCS, Candiolo, 10060 Turin, ItalyDepartment of Health Sciences (DISSAL), Section of Biostatistics, University of Genova, 16100 Genova, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16100 Genova, ItalyDepartment of Biosciences, COMT-Centre for Molecular and Translational Oncology, University of Parma, 43124 Parma, ItalyDivision of Urology, Department of Surgery, Dentistry, Paediatrics and Gynaecology, University and Hospital Trust of Verona, 37134 Verona, ItalyWe 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 (<i>p</i> = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes (<i>p</i> = 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 (<i>p</i> = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.https://www.mdpi.com/2075-4426/12/5/727clear cell renal cell carcinomatumor samplingintratumoral heterogeneityangiogenesisimmunityimmunohistochemistry |
| spellingShingle | Matteo Brunelli Guido Martignoni Giorgio Malpeli Alessandro Volpe Luca Cima Maria Rosaria Raspollini Mattia Barbareschi Alessandro Tafuri Giulia Masi Luisa Barzon Serena Ammendola Manuela Villanova Maria Angela Cerruto Michele Milella Sebastiano Buti Melissa Bersanelli Giuseppe Fornarini Sara Elena Rebuzzi Valerio Gaetano Vellone Gabriele Gaggero Giuseppe Procopio Elena Verzoni Sergio Bracarda Martina Fanelli Roberto Sabbatini Rodolfo Passalacqua Bruno Perrucci Maria Olga Giganti Maddalena Donini Stefano Panni Marcello Tucci Veronica Prati Cinzia Ortega Anna Caliò Albino Eccher Filippo Alongi Giovanni Pappagallo Roberto Iacovelli Alessandra Mosca Paolo Umari Ilaria Montagnani Stefano Gobbo Francesco Atzori Enrico Munari Marco Maruzzo Umberto Basso Francesco Pierconti Carlo Patriarca Piergiuseppe Colombo Alberto Lapini Giario Conti Roberto Salvioni Enrico Bollito Andrea Cossarizza Francesco Massari Mimma Rizzo Renato Franco Federica Zito-Marino Yoseba Aberasturi Plata Francesca Galuppini Marta Sbaraglia Matteo Fassan Angelo Paolo Dei Tos Maurizio Colecchia Holger Moch Maurizio Scaltriti Camillo Porta Brett Delahunt Gianluca Giannarini Roberto Bortolus Pasquale Rescigno Giuseppe Luigi Banna Alessio Signori Miguel Angel Llaja Obispo Roberto Perris Alessandro Antonelli Validation of a Novel Three-Dimensional (<i>3D Fusion</i>) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 Study Journal of Personalized Medicine clear cell renal cell carcinoma tumor sampling intratumoral heterogeneity angiogenesis immunity immunohistochemistry |
| title | Validation of a Novel Three-Dimensional (<i>3D Fusion</i>) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 Study |
| title_full | Validation of a Novel Three-Dimensional (<i>3D Fusion</i>) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 Study |
| title_fullStr | Validation of a Novel Three-Dimensional (<i>3D Fusion</i>) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 Study |
| title_full_unstemmed | Validation of a Novel Three-Dimensional (<i>3D Fusion</i>) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 Study |
| title_short | Validation of a Novel Three-Dimensional (<i>3D Fusion</i>) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 Study |
| title_sort | validation of a novel three dimensional i 3d fusion i gross sampling protocol for clear cell renal cell carcinoma to overcome intratumoral heterogeneity the meet uro 18 study |
| topic | clear cell renal cell carcinoma tumor sampling intratumoral heterogeneity angiogenesis immunity immunohistochemistry |
| url | https://www.mdpi.com/2075-4426/12/5/727 |
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yosebaaberasturiplata validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study AT francescagaluppini validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study AT martasbaraglia validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study AT matteofassan validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study AT angelopaolodeitos validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study AT mauriziocolecchia validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study AT holgermoch validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study AT maurizioscaltriti validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study AT camilloporta validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study AT brettdelahunt validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study AT gianlucagiannarini validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study AT robertobortolus validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study AT pasqualerescigno validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study AT giuseppeluigibanna validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study AT alessiosignori validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study AT miguelangelllajaobispo validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study AT robertoperris validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study AT alessandroantonelli validationofanovelthreedimensionali3dfusionigrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study |