TIMP-3和mtp53在非小细胞肺癌中的表达及意义

背景与目的基质金属蛋白酶组织抑制剂-3(tissue inhibitor of metalloproteinases-3,TIMP-3)可通过多种途径调节肿瘤的浸润和转移,且可能与突变型p53(mutant-type p53,mtp53)存在一定的相关性。本研究旨在利用组织芯片技术检测TIMP-3和mtp53在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织及其淋巴结转移癌中的表达并探讨其意义。方法应用免疫组织化学LSAB法和Elivision法检测24例良性病变肺支气管黏膜上皮组织(对照组)、288例NSCLC组织(原发灶)及106例淋巴结转移灶癌组织(转移灶)中TIMP-3和mtp53的表达。结果原发灶与转移灶中TIMP-3的表达明显低于对照组(P<0.001),而mtp53的表达明显高于对照组(P<0.001);TIMP-3和mtp53在伴有/不伴有淋巴结转移的原发灶中的表达差异有统计学意义(P=0.015,P=0.030)。TIMP-3的表达与NSCLC的病理学分级有关(P=0.030),mtp53的表达与NSCLC的TNM分期和组织学类型有关(P=0.016,P=0.004)。TIMP-3与mtp53在原发灶中的表达呈负相关(P=0.008),其表达均与NSCLC患者的术后生存率有关(P=0.011,P=0.003)。结论 TIMP-3的低表达和mtp53的高表达都可促进肺癌的转移,且二者在肺癌转移中相互抑制,可能成为研究NSCLC转移机制的新靶点。

Expressions and Significance of TIMP-3 and mtp53 in Non-small Cell Lung Cancer

Background and objective Tissue inhibitor of metalloproteinase-3(TIMP-3) can regulate tumor infiltration and metastasis through multiple channels and is likely associated with mutant-type pS3(mtp53).This study detected the expressions of TIMP-3 and mtp53 in non-small cell lung cancer(NSCLC) and lymph node metastasis using tissue microarray and evaluated their significance.Methods TIMP-3 and mtp53 expressions were detected in 288 cases of NSCLC (NSCLC group),106 cases of metastatic carcinoma in lymph nodes(metastasis group),and 24 cases of benign lesions in the bronchial mucosa epithelium(control group) by immunohistochemical staining(LSAB and Elivision).Results The expression of TIMP-3 in the NSCLC and metastasis groups was lower than that in the control group(P<0.001),but the reverse was true for the expression of mtpS3(P<0.001).TIMP-3 and mtp53 expressions differed between NSCLC with(P=0.015) and without(P=0.030) lymph node metastasis.TIMP-3 expression correlated with NSCLC grade(P=0.030),whereas mtp53 expression correlated with TNM stage(P=0.016) and NSCLC histological type(P=0.004).Moreover,the expressions of TIMP-3 and mtpS3 were negative in NSCLC cases(P=0.008) and correlated with patient survival(P=0.011 and P=0.003,respectively). Conclusion Low expression of TIMP-3 and high expression of mtp53 in NSCLC can promote tumor metastasis and inhibit each other.TIMP-3 and mtp53 are promising targets for studying the metastatic mechanism of NSCLC.