Intraductal carcinoma of the prostate is a marker of aggressive disease. However, intraductal carcinoma exists on a morphologic continuum with high-grade prostatic intraepithelial neoplasia (PIN) and distinguishing intraductal carcinoma from PIN is a common diagnostic dilemma with significant clinical implications. We evaluated whether immunostains for PTEN and ERG can sensitively identify intraductal carcinoma and accurately distinguish it from high-grade PIN. A combined immunostain for PTEN, ERG, p63 and CK903 was developed and validated. Radical prostatectomy specimens with lesions meeting criteria for intraductal carcinoma (n=45), intraductal cribriform proliferations falling short of intraductal carcinoma (n=15), and PIN lesions (n=39) were retrospectively identified and assessed for PTEN and ERG. Cytoplasmic PTEN loss was identified in 84% (38/45) of the intraductal carcinoma and 100% (15/15) of intraductal cribriform proliferation cases. In contrast, cytoplasmic PTEN loss was never observed in PIN (0/39; P<0.0001). Of the 53 cases of intraductal carcinoma or intraductal cribriform proliferation with cytoplasmic PTEN loss, it was homogeneously lost in 42 cases (79%). Weak, focal nuclear positivity for PTEN was retained in 31 of these 42 cases (74%). ERG expression was identified in 58% (26/45) of intraductal carcinoma and 67% (10/15) of intraductal cribriform proliferations compared with 13% (5/39) of PIN. Concordance between the PTEN/ERG status of the intraductal carcinoma lesions and the concurrent invasive carcinoma was high (>95% and P<0.0001 for each), and substantially less for PIN and the concurrent invasive tumor (83% for PTEN and 67% for ERG; P=NS for each). Cytoplasmic PTEN loss occurs in the majority of intraductal carcinoma and intraductal cribriform proliferation cases. Cytoplasmic PTEN loss was never observed in PIN (100% specificity). Our study identifies PTEN loss as a potentially useful marker to distinguish intraductal carcinoma from PIN and provides a plausible molecular explanation for why intraductal carcinoma is associated with poor prognosis.

译文

前列腺导管内癌是侵袭性疾病的标志。然而,导管内癌存在于高度前列腺上皮内瘤变 (PIN) 的形态连续体上,将导管内癌与PIN区分开是一个常见的诊断难题,具有重要的临床意义。我们评估了PTEN和ERG的免疫染色是否可以敏感地识别导管内癌并将其与高级别PIN区分开。开发并验证了PTEN,ERG,p63和CK903的联合免疫染色。回顾性鉴定了符合导管内癌 (n = 45),导管内筛状增生低于导管内癌 (n = 15) 和PIN病变 (n = 39) 的前列腺癌根治术标本,并评估了PTEN和ERG。在导管内癌的84% (38/45) 和导管内筛状增殖病例的100% (15/15) 中发现了细胞质PTEN丢失。相反,在PIN中从未观察到细胞质PTEN丢失 (0/39; P<0.0001)。53例导管内癌或导管内筛状增生伴细胞质PTEN丢失,42例 (79%) 均匀丢失。在这42例中,有31例 (74% 例) 保留了PTEN的弱局灶性核阳性。与PIN的13% (5/39) 相比,在导管内癌的58% (26/45) 和导管内筛状增生的67% (10/15) 中鉴定了ERG表达。导管内癌病变与并发浸润性癌的PTEN/ERG状态之间的一致性较高 (每个均> 95% 且P<0.0001),而PIN与并发浸润性肿瘤的一致性较小 (PTEN 83%,ERG 67%; P = NS)。细胞质PTEN丢失发生在大多数导管内癌和导管内筛状增生病例中。在PIN中从未观察到细胞质PTEN丢失 (100% 特异性)。我们的研究确定PTEN丢失是区分导管内癌和PIN的潜在有用标记,并为为什么导管内癌与不良预后相关提供了合理的分子解释。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录