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MMP-3与细胞外MMP诱导因子在乳腺良、恶性病变中的表达及意义
刘岩1,袁媛2,马立人3*,邢朝斌4,费乐学5
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(1.华北煤炭医学院生物科学系生物化学与分子生物学学科,唐山 063000;2.临床医学系2004级1班;3. 生物科学系病原生物学与免疫学学科;4. 生物科学系普通生物学学科;5. 附属开滦医院普通外科)
摘要:
目的:检测基质金属蛋白酶3(matrix metalloproteinase3,MMP3)和细胞外基质金属蛋白酶诱导因子(extracellular matrix metalloproteinase inducer,EMMPRIN)在乳腺良、恶性病变组织中的表达和意义。方法:应用免疫组化二步法,检测58例乳腺癌,28例乳腺癌前病变、40例增生性病变、40例良性肿瘤及20例正常乳腺组织中MMP3和EMMPRIN蛋白的表达,并采用原位杂交法检测各种病变及正常乳腺组织各20例中MMP3 mRNA、EMMPRIN mRNA的表达,分析各指标的积分光密度(integral optic density ,IOD)值。结果:镜下观察可见MMP3、EMMPRIN及MMP3 mRNA、EMMPRIN mRNA在癌和癌前病变中的表达均较增生性病变、良性肿瘤及正常乳腺组织强。MMP3、EMMPRIN及MMP3 mRNA、EMMPRIN mRNA在癌和癌前病变组中的IOD值较增生性病变、良性肿瘤及正常乳腺组织组高(P<0.01),且在后3组中的表达差异无统计学意义。MMP3、EMMPRIN和MMP3 mRNA、EMMPRIN mRNA在癌和癌前病变组中的表达水平差异均无统计学意义。EMMPRIN蛋白在乳腺癌伴腋下淋巴结转移组的表达高于无淋巴结转移组(P<0.05)。在各病变组中,MMP3 mRNA与EMMPRIN mRNA的表达呈正相关,但MMP3和EMMPRIN蛋白的相关性在不同病变中有所不同。结论:MMP3、EMMPRIN过表达在乳腺癌前病变向癌转变的过程中可能起重要作用。EMMPRIN高表达的乳腺癌患者更易发生腋下淋巴结转移。
关键词:  乳腺肿瘤  细胞外基质金属蛋白酶诱导因子  基质金属蛋白酶-3
DOI:10.3724/SP.J.1008.2007.01188
投稿时间:2007-01-21
基金项目:河北省科技攻关项目(03276422).
Expression of MMP-3 and extracellular matrix metalloproteinase inducer in benign and malignant breast lesions
LIU Yan1,YUAN Yuan2,MA Li-ren3*,XING Zhao-bin4,FEI Le-xue5
(1. Division of Biochemistry and Molecular Biology, Department of Bioscience, North China Coal Medical College, Tangshan 063000, China;2. Student of 2004 Grade Class 1,Department of Clinical Medicine, North China Coal Medical College;3. Division of Pathogen and Immunology, Department of Bioscience, North China Coal Medical College;4. Division of Biology, Department of Bioscience, North China Coal Medical College;5.Department of General Surgery, Kailuan Hospital,North China Coal Medical College)
Abstract:
Objective:To explore the expression of MMP3 and extracellular matrix metalloproteinase inducer (EMMPRIN) in benign and malignant breast lesions and its relevance. Methods: Using immunohistochemical method, we examined the expression of MMP3 and EMMPRIN proteins in 58 breast cancer specimens,28 premalignant lesions, 40 hyperplasia specimens, 40 benign tumor specimens and 20 normal breast tissues. The expression of MMP3 mRNA and EMMPRIN mRNA was examined using in situ hybridization in 20 breast cancer specimens,20 premalignant lesions, 20 hyperplasia specimens, 20 benign tumor specimens and 20 normal breast tissues. The values of integral optic density (IOD)of the expression was calculated by image analysis system. Results: The expression of MMP3 and EMMPRIN proteins and mRNA was stronger in breast cancer and premalignant lesions than in the other lesions. The IODs of MMP3 and EMMPRIN proteins and mRNA in breast cancer and premalignant lesion were significantly higher than those of hyperplasia, benign tumors and normal breast tissues(P<0.01); there was no significant differences between the first 2 groups and between the last 3 groups. Expression of EMMPRIN in breast cancer patients with lymphatic metastasis was higher than those without lymphatic metastasis (P<0.05). MMP3 mRNA expression was positively correlated with EMMPRIN mRNA expression in all groups, but the correlation between expression of MMP3 and EMMPRIN proteins was different in different groups. Conclusion: Overexpression of MMP3 and EMMPRIN may play an important role in the malignant transformation of breast lesions. Patients with high expression of EMMPRIN are more likely to have lymphatic metastasis.
Key words:  breast neoplasms  extracellular matrix metalloproteinase inducer  matrix metalloproteinase 3