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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

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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Autores principales: Brunelli, Matteo, Martignoni, Guido, Malpeli, Giorgio, Volpe, Alessandro, Cima, Luca, Raspollini, Maria Rosaria, Barbareschi, Mattia, Tafuri, Alessandro, Masi, Giulia, Barzon, Luisa, Ammendola, Serena, Villanova, Manuela, Cerruto, Maria Angela, Milella, Michele, Buti, Sebastiano, Bersanelli, Melissa, Fornarini, Giuseppe, Rebuzzi, Sara Elena, Vellone, Valerio Gaetano, Gaggero, Gabriele, Procopio, Giuseppe, Verzoni, Elena, Bracarda, Sergio, Fanelli, Martina, Sabbatini, Roberto, Passalacqua, Rodolfo, Perrucci, Bruno, Giganti, Maria Olga, Donini, Maddalena, Panni, Stefano, Tucci, Marcello, Prati, Veronica, Ortega, Cinzia, Caliò, Anna, Eccher, Albino, Alongi, Filippo, Pappagallo, Giovanni, Iacovelli, Roberto, Mosca, Alessandra, Umari, Paolo, Montagnani, Ilaria, Gobbo, Stefano, Atzori, Francesco, Munari, Enrico, Maruzzo, Marco, Basso, Umberto, Pierconti, Francesco, Patriarca, Carlo, Colombo, Piergiuseppe, Lapini, Alberto, Conti, Giario, Salvioni, Roberto, Bollito, Enrico, Cossarizza, Andrea, Massari, Francesco, Rizzo, Mimma, Franco, Renato, Zito-Marino, Federica, Aberasturi Plata, Yoseba, Galuppini, Francesca, Sbaraglia, Marta, Fassan, Matteo, Dei Tos, Angelo Paolo, Colecchia, Maurizio, Moch, Holger, Scaltriti, Maurizio, Porta, Camillo, Delahunt, Brett, Giannarini, Gianluca, Bortolus, Roberto, Rescigno, Pasquale, Banna, Giuseppe Luigi, Signori, Alessio, Obispo, Miguel Angel Llaja, Perris, Roberto, Antonelli, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147893/
https://www.ncbi.nlm.nih.gov/pubmed/35629151
http://dx.doi.org/10.3390/jpm12050727
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author Brunelli, Matteo
Martignoni, Guido
Malpeli, Giorgio
Volpe, Alessandro
Cima, Luca
Raspollini, Maria Rosaria
Barbareschi, Mattia
Tafuri, Alessandro
Masi, Giulia
Barzon, Luisa
Ammendola, Serena
Villanova, Manuela
Cerruto, Maria Angela
Milella, Michele
Buti, Sebastiano
Bersanelli, Melissa
Fornarini, Giuseppe
Rebuzzi, Sara Elena
Vellone, Valerio Gaetano
Gaggero, Gabriele
Procopio, Giuseppe
Verzoni, Elena
Bracarda, Sergio
Fanelli, Martina
Sabbatini, Roberto
Passalacqua, Rodolfo
Perrucci, Bruno
Giganti, Maria Olga
Donini, Maddalena
Panni, Stefano
Tucci, Marcello
Prati, Veronica
Ortega, Cinzia
Caliò, Anna
Eccher, Albino
Alongi, Filippo
Pappagallo, Giovanni
Iacovelli, Roberto
Mosca, Alessandra
Umari, Paolo
Montagnani, Ilaria
Gobbo, Stefano
Atzori, Francesco
Munari, Enrico
Maruzzo, Marco
Basso, Umberto
Pierconti, Francesco
Patriarca, Carlo
Colombo, Piergiuseppe
Lapini, Alberto
Conti, Giario
Salvioni, Roberto
Bollito, Enrico
Cossarizza, Andrea
Massari, Francesco
Rizzo, Mimma
Franco, Renato
Zito-Marino, Federica
Aberasturi Plata, Yoseba
Galuppini, Francesca
Sbaraglia, Marta
Fassan, Matteo
Dei Tos, Angelo Paolo
Colecchia, Maurizio
Moch, Holger
Scaltriti, Maurizio
Porta, Camillo
Delahunt, Brett
Giannarini, Gianluca
Bortolus, Roberto
Rescigno, Pasquale
Banna, Giuseppe Luigi
Signori, Alessio
Obispo, Miguel Angel Llaja
Perris, Roberto
Antonelli, Alessandro
author_facet Brunelli, Matteo
Martignoni, Guido
Malpeli, Giorgio
Volpe, Alessandro
Cima, Luca
Raspollini, Maria Rosaria
Barbareschi, Mattia
Tafuri, Alessandro
Masi, Giulia
Barzon, Luisa
Ammendola, Serena
Villanova, Manuela
Cerruto, Maria Angela
Milella, Michele
Buti, Sebastiano
Bersanelli, Melissa
Fornarini, Giuseppe
Rebuzzi, Sara Elena
Vellone, Valerio Gaetano
Gaggero, Gabriele
Procopio, Giuseppe
Verzoni, Elena
Bracarda, Sergio
Fanelli, Martina
Sabbatini, Roberto
Passalacqua, Rodolfo
Perrucci, Bruno
Giganti, Maria Olga
Donini, Maddalena
Panni, Stefano
Tucci, Marcello
Prati, Veronica
Ortega, Cinzia
Caliò, Anna
Eccher, Albino
Alongi, Filippo
Pappagallo, Giovanni
Iacovelli, Roberto
Mosca, Alessandra
Umari, Paolo
Montagnani, Ilaria
Gobbo, Stefano
Atzori, Francesco
Munari, Enrico
Maruzzo, Marco
Basso, Umberto
Pierconti, Francesco
Patriarca, Carlo
Colombo, Piergiuseppe
Lapini, Alberto
Conti, Giario
Salvioni, Roberto
Bollito, Enrico
Cossarizza, Andrea
Massari, Francesco
Rizzo, Mimma
Franco, Renato
Zito-Marino, Federica
Aberasturi Plata, Yoseba
Galuppini, Francesca
Sbaraglia, Marta
Fassan, Matteo
Dei Tos, Angelo Paolo
Colecchia, Maurizio
Moch, Holger
Scaltriti, Maurizio
Porta, Camillo
Delahunt, Brett
Giannarini, Gianluca
Bortolus, Roberto
Rescigno, Pasquale
Banna, Giuseppe Luigi
Signori, Alessio
Obispo, Miguel Angel Llaja
Perris, Roberto
Antonelli, Alessandro
author_sort Brunelli, Matteo
collection PubMed
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 (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.
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spelling pubmed-91478932022-05-29 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 Brunelli, Matteo Martignoni, Guido Malpeli, Giorgio Volpe, Alessandro Cima, Luca Raspollini, Maria Rosaria Barbareschi, Mattia Tafuri, Alessandro Masi, Giulia Barzon, Luisa Ammendola, Serena Villanova, Manuela Cerruto, Maria Angela Milella, Michele Buti, Sebastiano Bersanelli, Melissa Fornarini, Giuseppe Rebuzzi, Sara Elena Vellone, Valerio Gaetano Gaggero, Gabriele Procopio, Giuseppe Verzoni, Elena Bracarda, Sergio Fanelli, Martina Sabbatini, Roberto Passalacqua, Rodolfo Perrucci, Bruno Giganti, Maria Olga Donini, Maddalena Panni, Stefano Tucci, Marcello Prati, Veronica Ortega, Cinzia Caliò, Anna Eccher, Albino Alongi, Filippo Pappagallo, Giovanni Iacovelli, Roberto Mosca, Alessandra Umari, Paolo Montagnani, Ilaria Gobbo, Stefano Atzori, Francesco Munari, Enrico Maruzzo, Marco Basso, Umberto Pierconti, Francesco Patriarca, Carlo Colombo, Piergiuseppe Lapini, Alberto Conti, Giario Salvioni, Roberto Bollito, Enrico Cossarizza, Andrea Massari, Francesco Rizzo, Mimma Franco, Renato Zito-Marino, Federica Aberasturi Plata, Yoseba Galuppini, Francesca Sbaraglia, Marta Fassan, Matteo Dei Tos, Angelo Paolo Colecchia, Maurizio Moch, Holger Scaltriti, Maurizio Porta, Camillo Delahunt, Brett Giannarini, Gianluca Bortolus, Roberto Rescigno, Pasquale Banna, Giuseppe Luigi Signori, Alessio Obispo, Miguel Angel Llaja Perris, Roberto Antonelli, Alessandro J Pers Med Article 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. MDPI 2022-04-30 /pmc/articles/PMC9147893/ /pubmed/35629151 http://dx.doi.org/10.3390/jpm12050727 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Brunelli, Matteo
Martignoni, Guido
Malpeli, Giorgio
Volpe, Alessandro
Cima, Luca
Raspollini, Maria Rosaria
Barbareschi, Mattia
Tafuri, Alessandro
Masi, Giulia
Barzon, Luisa
Ammendola, Serena
Villanova, Manuela
Cerruto, Maria Angela
Milella, Michele
Buti, Sebastiano
Bersanelli, Melissa
Fornarini, Giuseppe
Rebuzzi, Sara Elena
Vellone, Valerio Gaetano
Gaggero, Gabriele
Procopio, Giuseppe
Verzoni, Elena
Bracarda, Sergio
Fanelli, Martina
Sabbatini, Roberto
Passalacqua, Rodolfo
Perrucci, Bruno
Giganti, Maria Olga
Donini, Maddalena
Panni, Stefano
Tucci, Marcello
Prati, Veronica
Ortega, Cinzia
Caliò, Anna
Eccher, Albino
Alongi, Filippo
Pappagallo, Giovanni
Iacovelli, Roberto
Mosca, Alessandra
Umari, Paolo
Montagnani, Ilaria
Gobbo, Stefano
Atzori, Francesco
Munari, Enrico
Maruzzo, Marco
Basso, Umberto
Pierconti, Francesco
Patriarca, Carlo
Colombo, Piergiuseppe
Lapini, Alberto
Conti, Giario
Salvioni, Roberto
Bollito, Enrico
Cossarizza, Andrea
Massari, Francesco
Rizzo, Mimma
Franco, Renato
Zito-Marino, Federica
Aberasturi Plata, Yoseba
Galuppini, Francesca
Sbaraglia, Marta
Fassan, Matteo
Dei Tos, Angelo Paolo
Colecchia, Maurizio
Moch, Holger
Scaltriti, Maurizio
Porta, Camillo
Delahunt, Brett
Giannarini, Gianluca
Bortolus, Roberto
Rescigno, Pasquale
Banna, Giuseppe Luigi
Signori, Alessio
Obispo, Miguel Angel Llaja
Perris, Roberto
Antonelli, Alessandro
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147893/
https://www.ncbi.nlm.nih.gov/pubmed/35629151
http://dx.doi.org/10.3390/jpm12050727
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AT obispomiguelangelllaja validationofanovelthreedimensional3dfusiongrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study
AT perrisroberto validationofanovelthreedimensional3dfusiongrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study
AT antonellialessandro validationofanovelthreedimensional3dfusiongrosssamplingprotocolforclearcellrenalcellcarcinomatoovercomeintratumoralheterogeneitythemeeturo18study