Small cell carcinoma of the prostate is a rare subtype with an aggressive
clinical course. Despite the frequent occurrence of ERG gene rearrangements in
acinar carcinoma, the incidence of these rearrangements in prostatic
small cell carcinoma is unclear. In addition, molecular markers to distinguish prostatic
small cell carcinomas from lung and bladder
small cell carcinomas may be clinically useful. We examined the occurrence of ERG gene rearrangements by fluorescence in situ hybridization in prostatic, bladder and lung
small cell carcinomas. We also examined the expression of ERG,
androgen receptor (AR) and NKX3-1 by immunohistochemistry in prostatic cases. Overall, 45% (10/22) of prostatic
small cell carcinoma cases harbored ERG rearrangements, whereas no cases of bladder or lung
small cell carcinomas showed ERG rearrangement (0/12 and 0/13, respectively). Of prostatic
small cell carcinoma cases, 80% (8/10) showed ERG deletion and 20% (2/10) showed ERG translocation. In 83% (5/6) of prostatic
small cell carcinoma cases in which a concurrent conventional prostatic
acinar carcinoma component was available for analysis, there was concordance for the presence/absence of ERG gene rearrangement between the different subtypes. ERG, AR and NKX3-1
protein expression was detected in a minority of prostatic
small cell carcinoma cases (23, 27 and 18%, respectively), while these markers were positive in the majority of concurrent
acinar carcinoma cases (66, 83 and 83%, respectively). The presence of ERG rearrangements in nearly half of the prostatic
small cell carcinomas is a similar rate of rearrangement to that found in prostatic
acinar carcinomas. Furthermore, the high concordance rate of ERG rearrangement between the small cell and acinar components in a given patient supports a common origin for these two subtypes of
prostate cancer. Finally, the absence of ERG rearrangement in bladder or lung
small cell carcinomas highlights the utility of detecting ERG rearrangement in
small cell carcinomas of unknown primary for establishing prostatic origin.