Pacheco M M, Mourão M, Mantovani E B, Nishimoto I N, Brentani M M
Fundação Oncocentro de São Paulo, Divisão de Oncologia Clínica e Laboratorial, SP, Brasil.
Clin Exp Metastasis. 1998 Oct;16(7):577-85. doi: 10.1023/a:1006580415796.
The purpose of this study was to investigate the association among matrix metalloproteinases (gelatinases A and B, stromelysin-3 (ST3) and matrilysin) mRNAs expressed in primary breast carcinomas and standard prognostic parameters and clinical outcome. mRNA levels were determined by Northern analysis in samples of 81 breast cancer patients (median follow-up, 40 months) and 27 samples of uninvolved adjacent breast tissue. Proteases were expressed by the majority of the tumors and normal breast tissues examined. ST3, gelatinase A and matrilysin mRNAs were more often expressed at high levels in carcinomatous than in normal breast tissues. Differences in the distribution of gelatinase B mRNA were not found. However, paired normal tissues generally produced weaker signals when compared to matched tumor samples. Univariate analysis showed no significant association of gelatinase A and matrilysin mRNAs with the classical prognostic markers (age, menopausal status, stage, size, nodal status, vascular infiltrate, necrosis, steroid receptors, metastasis and survival). Overexpression of ST3 was more frequently found in tumors of post-menopausal women (P < 0.022). Elevated expression of gel B mRNA was associated with the presence of vascular infiltrate (P < 0.026), necrosis (P < 0.039), PR negative tumors (P < 0.014) and inversely correlated to the number of survivors (P < 0.021). Multivariate analysis including 68 patients for whom all information was available indicated that neither stromelysin correlated significantly with pathological, clinical or biochemical features. High levels of gelatinase A and B mRNAs were inversely associated with the number of survivors. Our findings suggest that measurements of gelatinase A and B mRNAs expression in breast carcinoma may help to identify patients with an aggressive form of the disease.
本研究的目的是调查原发性乳腺癌中表达的基质金属蛋白酶（明胶酶A和B、基质溶解素-3（ST3）和基质溶素）mRNA与标准预后参数及临床结果之间的关联。通过Northern分析确定了81例乳腺癌患者样本（中位随访时间为40个月）和27例未受累的相邻乳腺组织样本中的mRNA水平。在所检测的大多数肿瘤和正常乳腺组织中均有蛋白酶表达。与正常乳腺组织相比，癌组织中ST3、明胶酶A和基质溶素mRNA更常高表达。未发现明胶酶B mRNA分布存在差异。然而，与匹配的肿瘤样本相比，配对的正常组织通常产生较弱的信号。单因素分析显示，明胶酶A和基质溶素mRNA与经典预后标志物（年龄、绝经状态、分期、大小、淋巴结状态、血管浸润、坏死、类固醇受体、转移和生存）无显著关联。绝经后女性肿瘤中更常发现ST3过表达（P < 0.022）。凝胶B mRNA表达升高与血管浸润（P < 0.026）、坏死（P < 0.039）、PR阴性肿瘤（P < 0.014）相关，且与存活者数量呈负相关（P < 0.021）。对68例可获得所有信息的患者进行的多因素分析表明，基质溶解素与病理、临床或生化特征均无显著相关性。高水平的明胶酶A和B mRNA与存活者数量呈负相关。我们的研究结果表明，检测乳腺癌中明胶酶A和B mRNA的表达可能有助于识别具有侵袭性疾病形式的患者。
