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.
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ICR Authors
Authors
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
Caliò, 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
Aberasturi Plata, Y
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
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
Caliò, 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
Aberasturi Plata, Y
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
Document Type
Journal Article
Date
2022-04-30
Date Accepted
2022-04-26
Date Available
2022-07-13T14:31:26Z
Abstract
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.
Citation
Journal of Personalized Medicine, 2022, 12 (5), pp. 727 -
Source Title
Journal of Personalized Medicine
Publisher
MDPI
ISSN
2075-4426
eISSN
2075-4426
2075-4426
2075-4426
Collections
Research Team
PrCa Targeted Therapy