ERG-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.
ERG-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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DOI：
10.1038/modpathol.2011.56
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发表时间：
2011-08
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前列腺癌是一种异质性疾病，具有多灶性和形态变异性。特别是前列腺小细胞癌是一种具有侵袭性的罕见变异。区分前列腺小细胞癌和膀胱小细胞癌可能具有挑战性，特别是在没有相关的前列腺腺癌或尿路上皮癌的小活检标本中。最近，ETS基因，特别是ETS相关基因（ERG）和跨膜蛋白酶丝氨酸2（TMPRSS 2）之间的基因融合已被确定为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。本文报告30例前列腺小细胞癌，其中13例合并前列腺腺癌。用3′/5′ ERG和TMPRSS 2探针混合物对福尔马林固定的石蜡包埋组织切片进行三色荧光原位杂交（FISH）。膀胱小细胞癌和常规前列腺腺癌（各25例）也作为对照进行了测试。ERG基因改变仅见于前列腺恶性肿瘤，而良性前列腺组织和膀胱小细胞癌中未发现。47%（14/30）的前列腺小细胞癌存在TMPRSS 2-ERG基因融合。在合并前列腺腺癌的病例中，85%（11/13）的两种成分表现相同。在20%的重排病例中，ERG异常与5′ ERG缺失有关。在17%（5/30）的病例中，存在21 q22位点的增益。2例小细胞癌和腺癌的畸变不一致，1例5′ ERG缺失，1例21号染色体获得，均为腺癌。前列腺小细胞癌表现出TMPRSS 2-ERG重排，其频率与前列腺腺癌相当。在同时发生腺癌和小细胞癌的病例中，大多数在两种成分中显示出相同的异常，表明可能存在共同的克隆起源。不一致的改变存在于罕见的情况下，这表明在多灶性肿瘤中获得额外的遗传变化可能是疾病进展为更具侵袭性表型的原因。TMPRSS 2-ERG融合在膀胱小细胞癌中不存在，支持FISH在区分前列腺和膀胱原发性肿瘤以及鉴定来源不明的转移性小细胞癌中的效用。
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.
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影响因子：
30.8
作者：
Carver, Brett S.;Tran, Jennifer;Gopalan, Anuradha;Chen, Zhenbang;Shaikh, Safa;Carracedo, Arkaitz;Alimonti, Andrea;Nardella, Caterina;Varmeh, Shohreh;Scardino, Peter T.;Cordon-Cardo, Carlos;Gerald, William;Pandolfi, Pier Paolo
通讯作者：
Pandolfi, Pier Paolo
影响因子：
11.2
作者：
Gopalan A;Leversha MA;Satagopan JM;Zhou Q;Al-Ahmadie HA;Fine SW;Eastham JA;Scardino PT;Scher HI;Tickoo SK;Reuter VE;Gerald WL
通讯作者：
Gerald WL
影响因子：
11.2
作者：
Iljin, Kristiina;Wolf, Maija;Kallioniemi, Olli
通讯作者：
Kallioniemi, Olli
影响因子：
11.2
作者：
Mehra, Rohit;Tomlins, Scott A.;Chinnaiyan, Arul M.
通讯作者：
Chinnaiyan, Arul M.
影响因子：
2.1
作者：
Barry, Marc;Perner, Sven;Rubin, Mark A.
通讯作者：
Rubin, Mark A.