Immunohistochemically detected IDH1R132H mutation is rare and mostly heterogeneous in prostate cancer
IDH1 mutations are oncogenic through induction of DNA damage and genome instability. They are of therapeutic interest because they confer increased sensitivity to radiation and cytotoxic therapy and hold potential for vaccination therapy.
In this study, we analyzed more than 17,000 primary prostate cancer tissues with a mutation-specific antibody for the IDH1R132H mutation.
IDH1 mutation-specific staining was found in 42 of 15,531 (0.3%) interpretable cancers. IDH1 mutation was associated with higher preoperative PSA and Gleason grade (p < 0.05, each) but was unrelated to PSA recurrence. A comparison with other molecular tumor features available from earlier studies revealed that TMPRSS2-ERG fusion as well as deletion of PTEN, 5q21, 6q15, and 3p13 was less frequent in IDH1-mutated than in non-mutated cancer. Increased lethality of genetically instable, “aberration-rich” cancer cells in the presence of IDH1 mutations could possibly explain this observation. Heterogeneity analysis revealed a homogeneous mutation in only 1 of 16 IDH1-mutated cancers. This high degree of heterogeneity may profoundly limit therapeutic targeting of IDH1 mutations in prostate cancer.
The data show that 0.3% of prostate cancers have an IDH1R132H mutation and that these are mostly heterogeneous. Once specific anti-IDH1 therapy becomes reality, only a very small group of prostate cancer patients may benefit from such a treatment.
KeywordsIDH1 ERG Deletion Prostate cancer TMA
RS, GS, and TS developed the project; AH, MB, MK, CMK, SS, AL, AA, CW, EN, CG, FB, SM, WW, FJ, TSC, TK and MCT collected data; AH, CHM, MK, RS and CS did data analysis; AH, MK, RS, GS and CS wrote the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare they have no conflict of interest.
The study was approved by the ethics committee Ärztekammer Hamburg (WF-049/09 and PV3652). The work has been carried out in compliance with the Helsinki Declaration.
According to local laws (HmbKHG, §12,1) informed consent was not necessary.