MET alterations in biphasic squamoid alveolar papillary renal cell carcinomas and clinicopathological features
| Autor: | Thomas, Denize, Pierre Alexandre, Just, Mathilde, Sibony, Hélène, Blons, Marc Olivier, Timsit, Tom, Drossart, Deborah, Jakubowicz, Chloé, Broudin, Aurélien, Morini, Thierry, Molina, Yann, Vano, Marie, Auvray-Kuentz, Stéphane, Richard, Arnaud, Mejean, Anne Paule, Gimenez Roqueplo, Nelly, Burnichon, Virginie, Verkarre |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Aged 80 and over Male Paris DNA Copy Number Variations DNA Mutational Analysis Gene Dosage High-Throughput Nucleotide Sequencing Middle Aged Proto-Oncogene Proteins c-met Immunohistochemistry Proto-Oncogene Mas Carcinoma Papillary Kidney Neoplasms Phenotype Mutation Biomarkers Tumor Humans Female Genetic Predisposition to Disease Carcinoma Renal Cell In Situ Hybridization Fluorescence Aged |
| Zdroj: | Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 34(3) |
| ISSN: | 1530-0285 |
| Popis: | Biphasic squamoid alveolar papillary renal cell carcinoma (BSA-PRCC) is a recently studied lesion considered a morphologic variant of papillary renal cell carcinoma (RCC), more closely related to type 1. Considering the role of proto-oncogene MET in both sporadic type 1 papillary RCC and hereditary papillary RCC, we aimed to explore the role of MET activation in the oncogenesis of BSA-PRCC. We identified 17 patients with either unique (n = 14) or multiple (n = 3) BSA-PRCC, all localized, and performed an integrative analysis of MET status in 18 formalin-fixed paraffin-embedded tumors combining next-generation sequencing analysis, fluorescent in situ hybridization and immunohistochemistry. Trisomy 7 was found in 86% of tumors (14/16) without MET amplification at 7q31 (15/15). A pathogenic MET genetic variant was identified in 60% (9/15) of cases, at the germline level in 57% (4/7) of tested patients or at the somatic level (5/11). MET expression was observed in all tumors with a higher value of combined score in large cells (mean 97%, range 80-100%) than in small cells (mean 74%, range 10-100%) and was lower in two cases without MET copy number gain. In conclusion, our study provides additional evidence to consider biphasic squamoid alveolar papillary RCC as a morphological variant of type 1 papillary renal RCC. Our data strongly suggest that MET represents a major oncogenic driver gene in BSA-PRCC, harboring a higher frequency of MET mutation that encourages to further explore the benefice of anti-MET targeted therapies for aggressive BSA-PRCC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink