Specific von Hippel-Lindau protein expression of clear cell renal cell carcinoma with "immunogenic" features

Abstract

Human clear cell renal cell carcinoma (CCRCC) is characterized by specific von Hippel-Lindau (VHL) gene alterations and immunogenic features. In the present study, the immunohistochemical expression of the von Hippel-Lindau gene protein (pVHL) was compared with the presence of major histocompatibility complex (MHC I-II), tumor infiltrating lymphocytes (TIL) and tumoral immune complexes (TIC) in CCRCC. Native tumor tissues of 132 RCC patients (95 with the common clear cell subtype), diagnosed according to the Heidelberg classification, were obtained for immunohistochemistry. Tumor stainings with pVHL, MHC I-II and tumor infiltrating lymphocytes (T and B lymphocytes, monocytes) were detected by immunoperoxidase methods using monoclonal antibodies. Tumoral immune complexes (IgG, IgA, IgM and C1q, C3 complement proteins) were visualized by fluorescent polyclonal antibodies. Immune stainings were semiquantitatively evaluated. Specificity and sensitivity of these markers in relation to the common histological subtype of RCC (CCRCC) were calculated. CCRCC was characterized by specific pVHL expression. At the same time, CCRCC was associated with constitutional MHC I-II expression and highly specific degree of TIL and TIC. It is concluded that specific pVHL expression of CCRCC is frequently associated with immunogenic features. Immunohistochemical analysis aims the initial tumor staging of RCC patients to achieve better patient selection for immunotherapy. However, the association of pVHL expression with the immunogenic CCRCC is statistically relevant, the mechanism and its clinical relevance in immunotherapy still remains to be tested.