Rb loss is characteristic of prostatic small cell neuroendocrine carcinoma.
Rb loss is characteristic of prostatic small cell neuroendocrine carcinoma.
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DOI：
10.1158/1078-0432.ccr-13-1982
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发表时间：
2014-02-15
期刊：
影响因子：
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通讯作者：
Lotan TL
中科院分区：
文献类型：
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作者：
Tan HL;Sood A;Rahimi HA;Wang W;Gupta N;Hicks J;Mosier S;Gocke CD;Epstein JI;Netto GJ;Liu W;Isaacs WB;De Marzo AM;Lotan TL
随着雄激素抑制药物的最新进展，前列腺癌的小细胞神经内分泌癌可能变得越来越常见。因此，开发前列腺癌小细胞分化的分子标志物对指导这种侵袭性肿瘤的诊断和治疗具有重要意义。采用免疫组织化学(IHC)、拷贝数改变分析和测序等方法，检测了RB1、TP53和PTEN在前列腺小细胞癌和腺泡癌中的表达情况。我们发现90%(26/29)的小细胞癌存在Rb蛋白缺失，85%(11/13)存在RB1等位基因缺失。在与前列腺小细胞癌同时发生的腺泡状瘤中，43%(3/7)的腺泡状细胞瘤Rb蛋白缺失。而在原发腺泡癌中仅有7%(10/150)、伴神经内分泌分化的原发腺泡癌中仅有11%(4/35)和转移性去势耐药腺泡癌中有15%(2/13)出现Rb蛋白缺失。小细胞癌中PTEN蛋白缺失率为63%(17/27)，其中38%(5/13)为等位基因缺失。免疫组化检测发现56%(14/25)的小细胞癌有P53基因积聚，其中60%(6/10)的小细胞癌有TP53基因突变。RB1基因缺失在前列腺小细胞癌中是一种常见的事件，可以通过验证的IHC法检测到。由于Rb蛋白丢失在高级别腺泡肿瘤中很少发生，这些数据表明Rb蛋白丢失在小细胞癌的发展过程中是一个关键事件，可能是一个有用的诊断和潜在的治疗靶点。
Small cell neuroendocrine carcinoma of the prostate is likely to become increasingly common with recent advances in pharmacologic androgen suppression. Thus, developing molecular markers of small cell differentiation in prostate cancer will be important to guide diagnosis and therapy of this aggressive tumor. We examined the status of RB1, TP53 and PTEN in prostatic small cell and acinar carcinomas via immunohistochemistry (IHC), copy number alteration analysis and sequencing of formalin fixed paraffin-embedded specimens. We found Rb protein loss in 90% (26/29) of small cell carcinoma cases with RB1 allelic loss in 85% (11/13) of cases. Of acinar tumors occurring concurrently with prostatic small cell carcinoma, 43% (3/7) showed Rb protein loss. In contrast, only 7% (10/150) of primary high grade acinar carcinomas, 11% (4/35) of primary acinar carcinomas with neuroendocrine differentiation, and 15% (2/13) of metastatic castrate resistant acinar carcinomas showed Rb protein loss. Loss of PTEN protein was seen in 63% (17/27) of small cell carcinomas, with 38% (5/13) showing allelic loss. By IHC, accumulation of p53 was observed in 56% (14/25) of small cell carcinomas, with 60% (6/10) of cases showing TP53 mutation. Loss of RB1 by deletion is a common event in prostatic small cell carcinoma and can be detected by validated IHC assay. As Rb protein loss rarely occurs in high grade acinar tumors, these data suggest that Rb loss is a critical event in the development of small cell carcinomas and may be a useful diagnostic and potential therapeutic target.