Glutathione S-transferase:: differential expression of α, μ, and π isoenzymes in benign prostate, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma
Glutathione S-transferase:: differential expression of α, μ, and π isoenzymes in benign prostate, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma
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DOI：
10.1016/j.humpath.2007.02.008
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发表时间：
2007-09-01
期刊：
影响因子：
3.3
通讯作者：
Shanks, Jonathan H.
中科院分区：
文献类型：
--
作者：
Bostwick, David G.;Meiers, Isabelle;Shanks, Jonathan H.
谷胱甘肽S-转移酶（GST）是一类对毒素和致癌物的灭活起关键作用的酶。我们检测了25例临床局限性前列腺癌根治术标本中GST多个亚类的细胞表达。Gleason评分范围为5 - 9，病理分期从pT 2a到pT 3b不等（均为N 0 M0）。抗体针对GST Ya、Yc和Yk（α亚类）、Yb 1（μ亚类）和YPr（pi亚类）。评估良性上皮、高级别前列腺上皮内瘤（PIN）和腺癌的阳性细胞百分比和染色强度。GST α（Ya）在良性腺泡中30%的细胞（平均值）、高级别PIN中4.9%的细胞和腺癌中4.5%的细胞中检测到。a（Yk）、p（Yb 1）和pi（Yp）的相应结果分别为12.7%、10.9%和3.5%; 8.7%、5.2%和0.6%;以及66.7%、0%和0%。GST-Yc（一个亚类）表达水平最低，在散在的良性分泌细胞中呈弥漫性弱染色，在高级别PIN和癌中仅单个细胞（< 1%）表达。这些结果表明，随着前列腺肿瘤从良性上皮向高级别PIN和癌的进展，GST的所有亚类表达一致减少或丧失。我们假设前列腺的致癌作用是由于多种GST和其他解毒和抗突变剂的表达减少或丧失而导致细胞对致突变剂的处理能力受损。(c)2007年爱思唯尔公司All rights reserved.
Glutathione S-transferases (GST) comprise a family of enzymes which are critical for inactivation of toxins and carcinogens. We examined the cellular expression of multiple subclasses of GST immunohistochemically in 25 radical prostatectomy specimens with clinically localized prostate cancer. Gleason scores ranged from 5 to 9, and pathologic stages varied from pT2a to pT3b (all N0M0). Antibodies were directed against GST Ya, Yc, and Yk (alpha subclass), Yb1 (mu subclass), and YPr (pi subclass). The percentage of positive cells and intensity of staining was assessed for benign epithelium, high-grade prostatic intraepithelial neoplasia (PIN), and adenocarcinoma. GST alpha (Ya) was detected in 30% of cells (mean) in benign acini, 4.9% of cells in high-grade PIN, and 4.5% of cells in adenocarcinoma. The corresponding results for a (Yk), p (Yb1), and pi (Yp) were 12.7%, 10.9%, and 3.5%; 8.7%, 5.2%, and 0.6%; and 66.7,% 0%, and 0%, respectively. GST Yc (a subclass) displayed the lowest level of expression, with diffuse weak staining in scattered benign secretory cells and only single cells (< 1%) in high-grade PIN and carcinoma. These results demonstrate consistent reduction or loss of expression of all subclasses of GST with progression of prostatic neoplasia from benign epithelium to high-grade PIN and carcinoma. We hypothesize that carcinogenesis in the prostate results from impaired cellular handling of mutagenic agents owing to reduction or loss of expression of multiple GST and other detoxifying and antimutagenesis agents. (c) 2007 Elsevier Inc. All rights reserved.