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首页> 外文期刊>Modern Pathology >ERG|[ndash]|TMPRSS2 rearrangement is shared by concurrent prostatic adenocarcinoma and prostatic small cell carcinoma and absent in small cell carcinoma of the urinary bladder: evidence supporting monoclonal origin
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ERG|[ndash]|TMPRSS2 rearrangement is shared by concurrent prostatic adenocarcinoma and prostatic small cell carcinoma and absent in small cell carcinoma of the urinary bladder: evidence supporting monoclonal origin

机译：ERG | ndash | TMPRSS2重排由并发的前列腺腺癌和前列腺小细胞癌所共有，而在膀胱小细胞癌中则不存在：支持单克隆起源的证据

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Prostatic carcinoma is a heterogeneous disease with frequent multifocality and variability in morphology. Particularly, prostatic small cell carcinoma is a rare variant with aggressive behavior. Distinction between small cell carcinoma of the prostate and urinary bladder may be challenging, especially in small biopsy specimens without associated prostatic adenocarcinoma or urothelial carcinoma. Recently, gene fusions between ETS genes, particularly ETS-related gene (ERG), and transmembrane protease, serine 2 (TMPRSS2) have been identified as a frequent event in prostate cancer. Thus, molecular methods may be helpful in determining the primary site of small cell carcinoma. Thirty cases of prostatic small cell carcinoma from the authors' archives were studied, among which 13 had concurrent prostatic adenocarcinoma. Tricolor fluorescence in situ hybridization (FISH) was performed on formalin-fixed paraffin-embedded tissue sections with a probe cocktail for 3′/5′ ERG and TMPRSS2. Cases of small cell carcinoma of the bladder and conventional prostatic adenocarcinoma (25 each) were also tested as controls. ERG gene alterations were found only in prostate malignancies and not in benign prostatic tissue or bladder small cell carcinoma. TMPRSS2–ERG gene fusion was found in 47% (14/30) of prostatic small cell carcinoma. Of cases with concurrent prostatic adenocarcinoma, 85% (11/13) had identical findings in both components. In 20% of rearranged cases, the ERG abnormality was associated with 5′ ERG deletion. In 17% (5/30) of cases, gain of the 21q22 locus was present. Two cases showed discordant aberrations in the small cell carcinoma and adenocarcinoma, one with deletion of 5′ ERG and one with gain of chromosome 21q, both in only the adenocarcinoma component. Small cell carcinoma of the prostate demonstrates TMPRSS2–ERG rearrangement with comparable frequency to prostatic adenocarcinoma. In cases with concurrent adenocarcinoma and small cell carcinoma, the majority showed identical abnormalities in both components, indicating a likely common clonal origin. Discordant alterations were present in rare cases, suggesting that acquisition of additional genetic changes in multifocal tumors may be responsible for disease progression to a more aggressive phenotype. TMPRSS2–ERG fusion is absent in bladder small cell carcinoma, supporting the utility of FISH in distinguishing prostate from bladder primary tumors and identifying metastatic small cell carcinoma of unknown origin.
机译：前列腺癌是一种异质性疾病，具有多灶性和形态变异性。特别地，前列腺小细胞癌是具有侵略行为的罕见变体。前列腺小细胞癌和膀胱癌之间的区别可能具有挑战性，尤其是在没有相关的前列腺腺癌或尿路上皮癌的小型活检标本中。最近，已经确定了ETS基因，特别是ETS相关基因（ERG）和跨膜蛋白酶丝氨酸2（TMPRSS2）之间的基因融合是前列腺癌中的常见事件。因此，分子方法可能有助于确定小细胞癌的原发部位。从作者的档案中研究了30例前列腺小细胞癌，其中13例并发前列腺腺癌。在福尔马林固定石蜡包埋的组织切片上进行三色荧光原位杂交（FISH），探针混合物用于3'/ 5'ERG和TMPRSS2。还测试了膀胱小细胞癌和常规前列腺腺癌（各25例）的病例作为对照。仅在前列腺恶性肿瘤中发现ERG基因改变，而在良性前列腺组织或膀胱小细胞癌中未发现ERG基因改变。在47％（14/30）的前列腺小细胞癌中发现了TMPRSS2-ERG基因融合。在并发前列腺腺癌的病例中，有85％（11/13）的患者在两个部位都有相同的发现。在20％的重排病例中，ERG异常与5'ERG缺失有关。在17％（5/30）的情况下，存在21q22基因座的增加。在小细胞癌和腺癌中，有2例显示出不一致的畸变，其中1例仅在腺癌成分中具有5'ERG缺失，而1例具有21q染色体获得。前列腺小细胞癌显示TMPRSS2-ERG重排，其频率与前列腺腺癌相当。在并发腺癌和小细胞癌的病例中，大多数在两个成分中均表现出相同的异常，表明可能是共同的克隆起源。在极少数情况下存在不一致的改变，这表明在多灶性肿瘤中获得其他遗传变化可能是疾病发展为更具攻击性的表型的原因。膀胱小细胞癌中不存在TMPRSS2-ERG融合，支持FISH区分前列腺癌与膀胱原发性肿瘤以及鉴定来源不明的转移性小细胞癌。

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