Alpert L C, Schecter R L, Berry D A, Melnychuk D, Peters W P, Caruso J A, Townsend A J, Batist G
McGill University Centre for Translational Research in Cancer, Lady Davis Research Institute, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, HST-1E2 Canada.
Clin Cancer Res. 1997 May;3(5):661-7.
Glutathione S-transferase (GST) represents a multifunctional enzyme family consisting of four known cytosolic isoforms (alpha, mu, pi, and Phi) that detoxify a variety of xenobiotic chemicals and may confer resistance to both chemotherapeutic drugs and carcinogens in various experimental models. GST-pi has already been extensively studied in clinical specimens, including breast cancer. We studied the immuno-histochemical distribution and relative immunopositivity of GST-alpha and GST-mu, based on a grading system for immunointensity, in samples of 51 neoplastic and 46 normal breast samples and 12 lymph node metastases from patients treated with intensive chemotherapy and bone marrow transplant. In normal breast tissue, GST-alpha localized predominantly to the cytoplasm of scattered cells lining the luminal aspects of the ducts. Occasional cells showed both cytoplasmic and nuclear GST-alpha immunoreactivity. GST-mu was stained in myoepithelial cells preferentially as well as in occasional ductal cells (including apocrine epithelium), vascular smooth muscle, and plasma cells. GST-alpha and GST-mu were detected in 22 of 51 (43%) and 24 of 48 (50%) invasive cancers, respectively. In paired samples of normal and malignant tissue from the same patient, GST-alpha immunostaining in cancers was significantly less intense compared to that of normal breast tissue in 13 of 41 (32%) cases. No such trend was found for GST-mu in paired samples. Neither GST-alpha nor GST-mu immunopositivity in tumor or nonneoplastic breast was found to correlate with relapse-free or overall survival in this clinical context; however, the apparent decreased expression of GST-alpha in malignant versus normal breast epithelial cells could have important implications in breast carcinogenesis.
谷胱甘肽S-转移酶（GST）是一个多功能酶家族，由四种已知的胞质同工型（α、μ、π和Phi）组成，这些同工型可使多种外源性化学物质解毒，并在各种实验模型中赋予对化疗药物和致癌物的抗性。GST-π已在包括乳腺癌在内的临床标本中得到广泛研究。我们基于免疫强度分级系统，研究了51例肿瘤性乳腺样本、46例正常乳腺样本以及12例接受强化化疗和骨髓移植患者的淋巴结转移样本中GST-α和GST-μ的免疫组织化学分布及相对免疫阳性情况。在正常乳腺组织中，GST-α主要定位于导管腔面内衬散在细胞的细胞质中。偶尔有细胞同时显示细胞质和细胞核的GST-α免疫反应性。GST-μ优先在肌上皮细胞中染色，偶尔也在导管细胞（包括大汗腺上皮）、血管平滑肌和浆细胞中染色。在51例浸润性癌中，分别有22例（43%）检测到GST-α，48例中有24例（50%）检测到GST-μ。在同一患者的正常和恶性组织配对样本中，41例中有13例（32%）癌症中的GST-α免疫染色强度明显低于正常乳腺组织。在配对样本中未发现GST-μ有这种趋势。在该临床背景下，未发现肿瘤或非肿瘤性乳腺中的GST-α或GST-μ免疫阳性与无复发生存率或总生存率相关；然而，恶性乳腺上皮细胞中GST-α表达明显降低可能对乳腺癌发生具有重要意义。
