目的 探讨雌激素受体(estrogen receptor ,ER)阴性乳腺癌中的神经胶质瘤致病因子1(glioma-associated oncogene homolog 1,Gli1)及基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)的表达及临床意义。方法 用免疫组化Envision法检测ER阴性乳腺癌组织中Gli1、MMP-9、 CD34的表达情况, 分析Gli1、MMP-9表达与CD34、肿瘤大小、淋巴转移、临床TNM分期、HER-2表达的关系。结果 ER阴性乳腺癌组织中,Gli1阴性(-)、低表达(+)、中表达(++)及高表达(+++)组的CD34分别为48.83±7.53、60.69±10.02、64.68±12.92和75.91±11.30; MMP-9分别为48.15±8.44、61.69±10.71、67.76±14.03、73.11±12.78,组间比较差异均有统计学意义(P<0.05)。ER阴性乳腺癌组织中Gli1、MMP-9表达与肿瘤大小、临床TNM分期呈正相关(P<0.05)。ER阴性乳腺癌组织中Gli1与MMP-9表达存在一定正相关性(r=0.462,P<0.01)。结论 Gli1与MMP-9表达呈正相关性,推测Gli1是ER阴性乳腺癌增殖途径中重要的调控节点之一。
Abstract
Objective To study the expression and clinical significance of glioma-associated oncogene homolog 1 (Gli1) and matrix metalloproteinases-9 (MMP-9) in estrogen-independent breast cancer. Methods The expression of Gli1 protein was examined by Envision immunohistochemistry, Gli1, MMP-9 and CD34 expression were examined in ER-negative breast cancer. The relationships between them and CD34, tumor size, TNM stages, lymph node metastasis, HER-2 expression in ER-negative breast cancer were analyzed. Results The expression of CD34 was enhanced by the expression of Gli1 and MMP-9 in ER-negative group(CD34 expression were 48.83±7.53,60.69±10.02,64.68±12.92,75.91±11.30 in different group of Gli1;CD34 expressions were 48.15±8.44,61.69±10.71,67.76±14.03,73.11±12.78 in different group of MMP-9), with significant differences (P<0.05). The expression of Gli1 and MMP-9 were correlated with tumor size and clinical TNM stages in ER-negative breast cancer (P<0.05). The expression of MMP-9 was also correlated with lymphatic metastasis (P<0.05). The correlation existed between the expression of Gli1 and MMP-9 in ER-negative breast cancer(r=0.462, P<0.01). Conclusions Clinical positive correlation exists between the expression of Gli1 and MMP-9, Gli1 is an important regulating point in estrogen-independent breast cancer growth way.
关键词
乳腺肿瘤 /
雌激素受体 /
免疫组织化学 /
Gli1 /
基质金属蛋白酶-9
Key words
breast cancer /
estrogen receptor /
immunohistochemistry /
Gli1 /
matrix metalloproteinases-9
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参考文献
[1] Kurebayashi J. Current clinical trials of endocrine therapy for breast cancer[J]. Breast Cancer,2007,14:200-214.
[2] Kwon Y J, Hurst D R, Steg A D, et al. Gli1 enhances migration and invasion via up-regulation of MMP-11 and promotes metastasis in ERalpha negative breast cancer cell lines[J]. Clin Exp Metastasis,2011,28:437-449.[3] Nagai S, Nakamura M, Yanai K, et al. Gli1 contributes to the invasiveness of pancreatic cancer through matrix metalloproteinase-9 activation[J]. Cancer Sci, 2008,99:1377-1384.
[4] Sinicrope F A, Ruan S B, Cleary K R,et al. bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis[J]. Cancer Res,1995,55:237-241.
[5] Ten H A, Bektas N, Von S S, et al. Expression of the glioma-associated oncogene homolog (GLI) 1 in human breast cancer is associated with unfavourable overall survival[J]. BMC Cancer, 2009,9:298.
[6] Cui W, Wang L H, Wen Y Y, et al. Expression and regulation mechanisms of Sonic Hedgehog in breast cancer[J]. Cancer Sci, 2010,101:927-933.
[7] Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors[J]. Breast Cancer Res Treat, 1995,36:169-180.
[8] Cohen M M.Nevoid basal cell carcinoma syndrome: molecular biology and new hypotheses[J]. Int J Oral Maxillofac Surg, 1999,28:216-223.
[9] Kubo M, Nakamura M, Tasaki A, et al. Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer[J]. Cancer Res, 2004,64:6071-6074.
[10] Zhao J, Chen G, Cao D, et al. Expression of Gli1 correlates with the transition of breast cancer cells to estrogen-independent growth[J]. Breast Cancer Res Treat, 2010,119:39-51.
[11] 赵洁莹,陈 欢,王 雁,等. 雌激素受体α在乳腺癌细胞中对Gli1转录活性和表达的影响[J]. 第二军医大学学报, 2009,30(11):1221-1224.
[12] Balduyck M, Zerimech F, Gouyer V, et al. Specific expression of matrix metalloproteinases 1, 3, 9 and 13 associated with invasiveness of breast cancer cells in vitro[J]. Clin Exp Metastasis, 2000,18:171-178.
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