Evaluation of folliculin detection by immunohistochemistry in Birt-Hogg-Dube associated kidney tumors

Abstract

Germline inactivating mutations in folliculin (FLCN) cause Birt-Hogg-Dube (BHD) syndrome, a rare autosomal dominant disorder predisposing to kidney tumors. Kidney tumors associated with BHD typically lack FLCN expression due to loss of heterozygosity. In this study we assessed the potential of four commercial anti-FLCN antibodies for immunohistochemistry, as currently no routine diagnostic FLCN stainings are performed in the clinic. Despite comprehensive testing, we could not identify a commercial anti-FLCN antibody that is reproducibly effective in immunohistochemical analyses of formalin-fixed paraffin-embedded tissue material. We propose that dedicated future efforts are required to develop a suitable antibody for diagnostic immunohistochemical stainings. The inclusion of FLCN expression status as part of standard renal tumor pathology may contribute to better analyses of the molecular pathology of BHD tumors and facilitate identification of BHD patients, improve their (genetic and clinical) counseling, and enable genetic testing of at risk relatives.