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Approximately 19 % of patients in our series showed simultaneous high PD-1/PD-L1 immunoscores, and were the best candidates for receiving targeted anti-PD-1/PD-L1 immunotherapy, as determined using a tissue based rationale.

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CD10 has been considered a useful marker in the diagnosis of renal carcinomas, because of its expression in clear cell and papillary renal cell carcinomas and its absence in chromophobe renal cell carcinomas. On the other hand, chromophobe renal cell carcinoma expresses parvalbumin, which is absent in clear cell and papillary renal cell carcinomas. To further address the relevance of these markers, we studied the expression of CD10 and parvalbumin in 42 samples of chromophobe renal cell carcinoma (seven of which had aggressive features, including invasion beyond the renal capsule, renal vein invasion, metastases, or sarcomatoid transformation), 75 clear cell renal cell carcinomas (eight metastatic) and 51 papillary renal cell carcinomas (two metastatic). CD10 was found in 100% of clear cell renal cell carcinomas, 63% of papillary renal cell carcinomas and in all metastatic cases of both types. At variance with previous studies, we found CD10 expression in from 30 to 90% of the neoplastic cells, in 11 of 42 (26%) chromophobe renal cell carcinomas. The CD10-positive cases included five of the seven (71%) chromophobe renal cell carcinoma with aggressive features. Statistical analysis showed significant association of CD10-positive tumors with clinicopathologic aggressiveness (P ¼ 0.003) and mitotic figures (P ¼ 0.04). Parvalbumin was strongly expressed in all primary and metastatic chromophobe renal cell carcinomas. Western blot analysis was utilized to confirm the expression of both CD10 and parvalbumin in chromophobe renal cell carcinomas. Keywords: chromophobe renal cell carcinoma; renal cell carcinoma; immunohistochemistry; CD10; parvalbumin The importance of distinguishing the different types of renal cell carcinoma is underscored by the fact that they have different prognoses. 1-3 CD10, a cell surface metalloproteinase localized to the proximal nephron of the normal adult kidney, 4 has been proposed as a useful tool in the differential diagnosis of renal epithelial neoplasms. [5][6][7] This molecule has been described as a positive immunohistochemical marker for the two most common types of kidney cancer, clear cell and papillary renal cell carcinomas. [5][6][7][8][9] Previous studies analyzing CD10 immunoreactivity in a total of 25 chromophobe renal cell carcinomas have found negative reactions, 5,7 whereas Holm-Nielsen et al 10 found CD10 expressed in all three chromophobe carcinomas studied and Higgins et al 11 found a positive reaction in one of three tumors tested. In this study we undertook to investigate CD10 and parvalbumin immunoreactivity in a large series of clear cell, papillary, and chromophobe renal cell carcinomas. Materials and methods Patients and Tissue SamplesWe studied the immunohistochemical expression of CD10 and parvalbumin in 75 clear cell renal cell carcinomas, 51 papillary renal cell carcinomas and 38 chromophobe renal cell carcinomas (including 36

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