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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

Lookup NU author(s): Dr Pasquale RescignoORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2022 by the authors. Licensee MDPI, Basel, Switzerland.We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clear-RCC). 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.


Publication metadata

Author(s): Brunelli M, Martignoni G, Malpeli G, Volpe A, Cima L, Raspollini MR, Barbareschi M, Tafuri A, Masi G, Barzon L, Ammendola S, Villanova M, Cerruto MA, Milella M, Buti S, Bersanelli M, Fornarini G, Rebuzzi SE, Vellone VG, Gaggero G, Procopio G, Verzoni E, Bracarda S, Fanelli M, Sabbatini R, Passalacqua R, Perrucci B, Giganti MO, Donini M, Panni S, Tucci M, Prati V, Ortega C, Calio A, Eccher A, Alongi F, Pappagallo G, Iacovelli R, Mosca A, Umari P, Montagnani I, Gobbo S, Atzori F, Munari E, Maruzzo M, Basso U, Pierconti F, Patriarca C, Colombo P, Lapini A, Conti G, Salvioni R, Bollito E, Cossarizza A, Massari F, Rizzo M, Franco R, Zito-Marino F, Plata YA, Galuppini F, Sbaraglia M, Fassan M, Dei Tos AP, Colecchia M, Moch H, Scaltriti M, Porta C, Delahunt B, Giannarini G, Bortolus R, Rescigno P, Banna GL, Signori A, Obispo MAL, Perris R, Antonelli A

Publication type: Article

Publication status: Published

Journal: Journal of Personalized Medicine

Year: 2022

Volume: 12

Issue: 5

Print publication date: 01/05/2022

Online publication date: 30/04/2022

Acceptance date: 26/04/2022

Date deposited: 08/11/2024

ISSN (electronic): 2075-4426

Publisher: MDPI

URL: https://doi.org/10.3390/jpm12050727

DOI: 10.3390/jpm12050727

Data Access Statement: Not applicable.


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Funding

Funder referenceFunder name
LILT—Lega Italiana per la Lotta ai Tumori

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