Cookson M S, Reuter V E, Linkov I, Fair W R
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
J Urol. 1997 Feb;157(2):673-6.
Glutathione S-transferase (GST) enzymes may prevent carcinogenesis through inactivation of reactive electrophiles by conjugation to reduced glutathione. Recently, it was reported that most prostate cancers fail to express GST-pi despite an abundant presence in benign prostate tissue, suggesting a common genetic alteration. To define its presence in prostate tissue, we evaluated GST-pi expression in a variety of prostate tissues.
Immunostaining with anti-GST-pi antibody was performed on 69 benign prostates, 44 malignant prostates, 12 incidental prostate carcinomas and 17 prostatic intraepithelial neoplasia (PIN) specimens. Specimens were evaluated for the presence and percent of GST-pi. Within benign tissue, GST-pi immunostaining was distinguished between basal cells and secretory acinar epithelium.
In benign epithelium, the basal cells demonstrated intense staining in all cases. The mean percent staining among the basal cells was 67% (R 40-90%). The acinar epithelium stained weakly positive in 94% (65/69) of specimens, however the mean percent staining was only 5% (R 0-25%). GST-pi was detected in only 3.5% (2/56) of the prostate cancers. No incidental prostate cancers and only one (6%) high grade PIN stained positive.
Our study confirms the absence of GST-pi expression in prostate cancer and high grade PIN. Furthermore, GST-pi expression correlates well with the basal cell phenotype, but not with benign epithelial cells. The lack of staining among prostate cancer cells may reflect the absence of a basal cell layer, suggesting that GST-pi is involved more in epithelial differentiation and questioning its role in the malignant transformation of prostatic acinar cells.
谷胱甘肽S-转移酶(GST)可通过将活性亲电试剂与还原型谷胱甘肽结合使其失活,从而预防癌症发生。最近有报道称,尽管GST-π在良性前列腺组织中大量存在,但大多数前列腺癌却未能表达该酶,这提示存在一种常见的基因改变。为明确其在前列腺组织中的存在情况,我们评估了多种前列腺组织中GST-π的表达。
用抗GST-π抗体对69例良性前列腺、44例恶性前列腺、12例偶发前列腺癌和17例前列腺上皮内瘤变(PIN)标本进行免疫染色。评估标本中GST-π的存在情况及百分比。在良性组织中,区分基底细胞和分泌性腺泡上皮的GST-π免疫染色情况。
在良性上皮中,所有病例的基底细胞均显示强染色。基底细胞的平均染色百分比为67%(范围40 - 90%)。94%(65/69)的标本腺泡上皮呈弱阳性染色,但平均染色百分比仅为5%(范围0 - 25%)。仅在3.5%(2/56)的前列腺癌中检测到GST-π。偶发前列腺癌均未检测到,仅1例(6%)高级别PIN呈阳性染色。
我们的研究证实前列腺癌和高级别PIN中不存在GST-π表达。此外,GST-π表达与基底细胞表型密切相关,但与良性上皮细胞无关。前列腺癌细胞中缺乏染色可能反映了基底细胞层的缺失,这表明GST-π更多地参与上皮分化,并对其在前列腺腺泡细胞恶性转化中的作用提出质疑。