乳腺癌组织MMP-2、MMP-9和TIMP-2蛋白表达与肿瘤的转移及预后

目的　探讨乳腺癌组织中基质金属蛋白酶 (MatrixMeralloproteinases,MMPS)和金属蛋白酶组织抑制物 (TissueInhibitorsofMeralloproteinases,TIMPS)基因表达与肿瘤发生、病理分级、转移及预后之间的关系。方法　采用免疫组化LSAB法对 5 0例具有完整临床资料的乳腺癌组织及 2 0例乳腺纤维腺瘤的组织标本分别进行MMP 2、MMP 9和TIMP 2标记检测。结果　 5 0例乳腺癌组织中MMP 2、MMP 9和TIMP 2的表达分别为 74 % (37/ 5 0 )、6 5 % (31/ 5 0 )和 5 6 % (2 8/ 5 0 ) ,而在癌旁组织及良性纤维腺瘤增生的导管上皮中大部分不着色 ,少部分有微弱的着色 ,三者的表达与肿瘤的发生明显相关 ;MMP 2的高表达与肿瘤的病理分级、淋巴结的转移及临床预后复发均呈明显的正相关 (P <0 .0 5 ) ,TIMP 2的高表达与病理分级 ,淋巴结转移及预后复发呈明显的负相关 (P <0 .0 5 ) ,但MMP 9的表达却与临床因素无明显相关性。结论　乳腺癌组织中MMP 2高表达预示着病人预后更差 ,比MMP 9对乳癌患者转移及预后更具有判断价值 ,评价MMP 2和TIMP 2之间的平衡有利于早期了解预后 ,且比单独采用MMP 2指标更有利于了解癌肿的进展及预后。

Is the expression of MMP-2, MMP-9, and TIMP-2 related to metastasis and recurrence of breast cancer

Objective To determine the presence and cellular location of matrix metalloproteinase MMP 2, MMP 9 and tissue inhibitor of metalloproteinase TIMP 2 in breast cancer. Methods The expression of MMP 2, MMP 9 and TIMP 2 was detected using immunohistochemistry on tissue sections from 50 breast cancer and 20 breast fibroadenoma patients.Intact clinical parameters were available for all patients.Results Immunostaining of MMP 2, MMP 9 and TIMP 2 in breast cancer tissue was observed in 74% (37/50), 65% (31/50) and 56% (28/50) respectively. A very weak immunostaining of these three antibodies was observed in only a few epithelia in the surrounding background breast tissue and fibroadenoma tissue. The presence of MMP 2, MMP 9 and TIMP 2 was significantly greater in breast cancer tissues compared with all other breast tissues. The high level of MMP 2 was associated with poorer differentiation, more lymph node metastasis and increased recurrence of breast cancer ( P <0.05). The high level of TIMP 2 correlate inversely with the tumor grade, metastasis and recurrence ( P <0.05). There was no link between expression of MMP 9 and any clinical parameter. Conclusion The study suggests that high expression of MMP 2 in breast cancer tissue may be associated with an unfavorable prognosis while high expression of TIMP 2 may correlate with longer disease free survival. The ratio of MMP 2 and TIMP 2 provides more predictive information and may be a strong prognostic indicator of breast cancer. Induction of TIMP 2 expression can be considered as a alternate therapy regiment to protect the patients from tumor recurrence and metastasis.