Utility of cytokeratin 7, S100A1 and caveolin-1 as immunohistochemical biomarkers to differentiate chromophobe renal cell carcinoma from renal oncocytoma.

Differentiation of chromophobe renal cell carcinoma (chRCC) from benign renal oncocytoma (RO) can be challenging especially when there are overlapping histological and morphological features. In this study we have investigated immunohistochemical biomarkers (cytokeratin 7/CK7, Caveolin-1/Cav-1 and S100 calcium-binding protein A1/S100A1) to aid in this difficult differentiation and attempted to validate their use in human renal tumour tissue to assess their discriminatory ability, particularly for chRCC and RO, in an Australian cohort of patients. Retrospective study was carried out of archived formalin-fixed paraffin-embedded renal tumours from tumour nephrectomy specimens of 75 patients: 30 chRCC, 15 RO and 30 clear cell RCC (ccRCC). Sections were cut and immunostained with specific polyclonal antibodies of CK7, Cav-1 and S100A1. Morphometry was used to determine expression patterns of the biomarkers using Aperio ImageScope. Results were assessed with student t-test and ANOVA with significance at P<0.05. From this cohort, male-to-female ratio was 1.9:1. Median age was 64 (45-88 years) and median tumour size was 3.8 cm (range, 1.2-18 cm). There were 47 (62.7%) T1, 7 T2, 20 T3 and one T4 stage of RCC; with 2 patients presenting with M1 stage. There was significantly higher CK7 expression in chRCC compared to RO (P=0.03), and chRCC also had a different staining pattern and higher expression of Cav-1 compared to RO. There was higher expression of S100A1 in RO compared to chRCC. Immunohistochemical staining and standard morphometry of CK7, Cav-1 and S100A1 can aid in the differentiation of chRCC and RO. This may guide clinicians in management of patients when faced with difficult diagnostic histological distinction between the two tumour subtypes.