Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Mod Pathol. 2011 Jun;24(6):820-8. doi: 10.1038/modpathol.2011.7. Epub 2011 Feb 18.
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.
前列腺小细胞癌是一种罕见的亚型，具有侵袭性的临床病程。尽管在腺癌中经常发生 ERG 基因重排，但这些重排在前列腺小细胞癌中的发生率尚不清楚。此外，区分前列腺小细胞癌与肺和膀胱小细胞癌的分子标志物可能在临床上有用。我们通过荧光原位杂交检查了前列腺、膀胱和肺小细胞癌中 ERG 基因重排的发生情况。我们还通过免疫组织化学检查了前列腺病例中 ERG、雄激素受体 (AR) 和 NKX3-1 的表达。总体而言，45%（22 例中的 10 例）前列腺小细胞癌病例存在 ERG 重排，而膀胱或肺小细胞癌病例均未显示 ERG 重排（0/12 和 0/13）。在前列腺小细胞癌病例中，80%（10 例中的 8 例）显示 ERG 缺失，20%（10 例中的 2 例）显示 ERG 易位。在 83%（6 例中的 5 例）可分析同时存在的常规前列腺腺癌成分的前列腺小细胞癌病例中，不同亚型之间 ERG 基因重排的存在/缺失存在一致性。少数前列腺小细胞癌病例检测到 ERG、AR 和 NKX3-1 蛋白表达（分别为 23%、27%和 18%），而这些标志物在大多数同时存在的腺癌病例中呈阳性（分别为 66%、83%和 83%）。近一半的前列腺小细胞癌存在 ERG 重排，这一重排率与前列腺腺癌相似。此外，在给定患者中，小细胞和腺泡成分之间 ERG 重排的高一致性率支持这两种前列腺癌亚型具有共同的起源。最后，膀胱或肺小细胞癌中不存在 ERG 重排突出了检测未知原发灶小细胞癌中 ERG 重排以确定前列腺起源的实用性。
