Immunohistochemical Demonstration of Isocitrate Dehydrogenase 1 (IDH1) Mutation in a Small Subset of Prostatic Carcinomas

Recent advances in genomic sequencing have resulted in the discovery of the somatic mutations of cytoplasmic isocitrate dehydrogenase 1 (IDH1) in human solid tumors such as gliomas. The most common IDH1 mutation affects codon 132 and results in the conversion of amino acid residue arginine (R) to histidine (H). This IDH1(R132H) mutation is associated with a genetic and clinical characteristic group of gliomas in terms of grade and prognosis. We investigated whether immunohistochemistry (IHC) using a monoclonal antibody against the IDH1(R132H) mutant protein could be used in routine surgical pathology for identification of the mutation in solid human tumors. A total of 549 solid human tumors were examined in tissue microarrays, including prostate, thyroid, renal cell, ovarian, endometrial, breast, colorectal, non-small cell lung carcinoma, melanomas, and gliomas. IHC detected the IDH1(R132H) mutation in 72% (13/18) anaplastic astrocytomas and 30% (3/10) astrocytomas; however, it failed to detect the mutation in 258 thyroid, 11 renal cell, 10 ovarian, 18 endometrial, 20 breast, 25 colorectal, 22 non-small cell lung carcinoma, 25 melanomas, and 8 thyroid follicular adenomas. In contrast, expression of the IDH1(R132H) mutation was noted in 3 of 118 (2.5%) prostate carcinomas. Western blotting and polymerase chain reaction-based sequencing confirmed the mutation in 2 prostate carcinomas. This study indicates that IHC is a reliable method for the pathologic identification of the IDH1(R132H) mutation in solid human cancers such as prostate carcinomas.