Incidence and Correlation of AKT and ERG Expressions in Japanese Prostate Cancer
Hiroyuki Takahashi, Bungo Furusato, Takahiro Kimura, Mioko Okayasu, Sainosuke Mizukami, Shin Egawa, Hiroshi Hano. The Jikei University School of Medicine, Tokyo, Japan
Background: As prostate cancer carcinogenesis, 2 major pathways have been advocated. The one is PTEN deletion-AKT phosphorylation/activation pathway. In the previous study, we have shown that overexpression of phosphorylated AKT (pAKT) is associated with higher tumor stage and Gleason score, namely an aggressive tumors. Gene fusions involving ERG oncogene has been highlighted as another pathway. ERG overexpression is detected in approximately half of the prostate cancer cases in the Western population, but the incidence is not yet well known in the Asian patients. Also, the correlation of these 2 pathways is not well understood to date.
Design: A total of 131 clinical prostate cancer foci in 49 regular specimens (RS) and 82 in the constructed tissue microarray (TMA) were evaluated. Immunohistochemistry was performed with anti-AKT (phosphorylation form specific) and expression was evaluated. For RS, intensity and distribution were evaluated as grade 0 (none), 1 (weak/<10% of the tumor), 2 (intermediate/10-49%), 3 (strong/>50%), 4 (very strong/>50%). Grades 2-4 were designated as expression (+). For the TMA, intensity was evaluated as negative (-), or positive (+). Immunohistochemistry was performed with anti-ERG and expression was evaluated as negative (-) or positive (+).
Results: In the RS and TMA, 24/49 cases (49.0%) and 36/82 cases (43.9%) showed positive with pAKT, respectively. Similarly, 8 cases (16.3%) and 15 cases (18.3%) showed positive with ERG in the RS and TMA, respectively. As a concordance of pAKT and ERG expression, only one case showed expression of both proteins in RS series and reverse-correlation between pAKT and ERG expressions was significant (p=0.02). In TMA series, concordance of these 2 protein expressions was not statistically significant.
Conclusions: Approximately, half of the Japanese cancer show pAKT expression and the incidence is quite similar between RS and TMA. On the other hand, ERG gene fusion seems to be a relatively rare event in the Japanese prostate cancer patients compared with the Western population. The PTEN/AKT pathway may play a major role in the carcinogenesis of the Japanese prostate cancer. It is suggestive that these 2 pathways seem to be independently working.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 1:00 PM
Poster Session II # 154, Monday Afternoon