Fisher Kurt W, Zhang Shaobo, Wang Mingsheng, Montironi Rodolfo, Wang Lisha, Baldrige Lee A, Wang Jonas Y, MacLennan Gregory T, Williamson Sean R, Lopez-Beltran Antonio, Cheng Liang
Department of Pathology, Indiana University School of Medicine, Indianapolis, Indiana.
Department of Urology, Institute of Pathological Anatomy and Histopathology, Polytechnic University of the Marche Region (Ancona), United Hospitals, Ancona, Italy.
Mol Carcinog. 2017 Mar;56(3):814-820. doi: 10.1002/mc.22535. Epub 2016 Aug 31.
T1a prostate cancers (cancer found incidentally in transurethral resection, <5% of the tissue) are indolent tumors of the transition zone. The overexpression of ERG and the inactivation of PTEN have been shown to be important drivers of carcinogenesis in large series of prostate cancer, but the genetics of transition zone tumors have not been well characterized. We evaluated the status of ERG and PTEN in formalin-fixed paraffin-embedded tissue using immunohistochemical and FISH analysis in 54 T1a transition zone tumors. The protein expression of ERG was determined using a rabbit monoclonal antibody and nuclear staining was scored as positive or negative. The genomic status of ERG was determined using three colored FISH using an ERG-TMPRSS2 tri-color probe set. The protein expression of PTEN was determined using a rabbit monoclonal antibody and cytoplasmic, and nuclear staining was scored as positive or negative. The genomic status of PTEN was determined using dual color FISH with a PTEN probe and a CEP10 probe. We found ERG rearrangement in 2 of 54 tumors (4%), one with protein overexpression by immunohistochemistry. PTEN inactivation was seen in 13 of 54 tumors (24%). Nine of the 13 PTEN alleles were inactivated by hemizygous deletion. No homozygous PTEN deletion was observed. PTEN deletion and ERG rearrangement were mutually exclusive. ERG rearrangement was rare compared to peripheral zone tumors and to PTEN inactivation in T1a transition zone tumors. © 2016 Wiley Periodicals, Inc.
T1a期前列腺癌(经尿道前列腺切除术偶然发现的癌症,占组织的<5%)是移行带的惰性肿瘤。在大量前列腺癌病例中,ERG的过表达和PTEN的失活已被证明是致癌作用的重要驱动因素,但移行带肿瘤的遗传学特征尚未得到很好的描述。我们在54例T1a期移行带肿瘤中,使用免疫组织化学和荧光原位杂交(FISH)分析评估福尔马林固定石蜡包埋组织中ERG和PTEN的状态。使用兔单克隆抗体测定ERG的蛋白表达,并将核染色评定为阳性或阴性。使用ERG-TMPRSS2三色探针组通过三色FISH测定ERG的基因组状态。使用兔单克隆抗体测定PTEN的蛋白表达,并将细胞质和核染色评定为阳性或阴性。使用PTEN探针和CEP10探针通过双色FISH测定PTEN的基因组状态。我们在54例肿瘤中的2例(4%)发现了ERG重排,其中1例通过免疫组织化学显示蛋白过表达。在54例肿瘤中的13例(24%)观察到PTEN失活。13个PTEN等位基因中的9个通过半合子缺失失活。未观察到纯合子PTEN缺失。PTEN缺失和ERG重排相互排斥。与外周带肿瘤以及T1a期移行带肿瘤中的PTEN失活相比,ERG重排很少见。© 2016威利期刊公司。