Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare and aggressive tumor affecting mostly younger patients. This is the first study to assess the expression of programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) in FH-RCC. Formalin-fixed paraffin-embedded samples from 13 FH-RCCs collected in an international multi-institutional study, were evaluated by immunohistochemistry (IHC) for PD-1/PD-L1 reactivity in tumor cells and tumor infiltrating lymphocytes (TILs). PD-1/PD-L1 expression was further evaluated by qPCR. By IHC, PD-1 was negative in tumor cells in all 13 cases. PD-L1 was positive in tumor cells in 2/13 cases, weak positive in 7/13, and negative in 4/13 cases, respectively. In TILs, PD-1 was positive in 1/13, weak positive in 3/13, and negative in 9/13 cases. In TILs, PD-L1 was weak positive by IHC in 5/13, and negative in 8/13 cases, respectively. qPCR confirmed the result for 2 of 3 IHC weak positive PD-1 samples. Of 7 IHC weak positive samples (in tumor cells), PD-L1 mRNA was detected in all 7 tumors. The majority of FH-RCCs did not express PD-1/PD-L1 by IHC, which was confirmed by molecular analysis. PD-1/PD-L1 expression in FH-RCC is restricted to a proportion of cases which may benefit from targeted therapies.
Annals of diagnostic pathology. 2017 Apr 24 [Epub]
Reza Alaghehbandan, Jan Stehlik, Kiril Trpkov, Cristina Magi-Galluzzi, Enric Condom Mundo, Maria Pane Foix, Daniel Berney, Mathilde Sibony, Saul Suster, Abbas Agaimy, Delia Perez Montiel, Kristyna Pivovarcikova, Kvetoslava Michalova, Ondrej Daum, Ondrej Ondic, Pavla Rotterova, Martin Dusek, Milan Hora, Michal Michal, Ondrej Hes
Department of Pathology, Faculty of Medicine, University of British Columbia, Royal Columbian Hospital, Vancouver, BC, Canada., Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Czech Republic., Calgary Laboratory Services, University of Calgary, Calgary, AB, Canada., Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA., Department of Pathology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain., Bart's Cancer Center, London, United Kingdom., Hospital Cochin, Paris, France., Department of Pathology, Medical College Wisconsin, Milwaukee, WI, USA., Department of Pathology, University Erlangen, Germany., Department of Pathology, Instituto Nacional de Cancerologia, Mexico City, Mexico., Department of Urology, Charles University, Medical Faculty and Charles University Hospital Plzen, Czech Republic., Department of Pathology, Charles University, Medical Faculty and Charles University Hospital Plzen, Czech Republic. Electronic address: .