Tissue and circulating immunoreactive protein for MMP-2 and TIMP-2 in head and neck squamous cell carcinoma -: tissue immunoreactivity predicts aggressive clinical course
Tissue and circulating immunoreactive protein for MMP-2 and TIMP-2 in head and neck squamous cell carcinoma -: tissue immunoreactivity predicts aggressive clinical course
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DOI：
10.1038/modpathol.3800506
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发表时间：
2006-02-01
期刊：
影响因子：
7.5
通讯作者：
Turpeenniemi-Hujanen, T
中科院分区：
文献类型：
--
作者：
Ruokolainen, H;Pääkkö, P;Turpeenniemi-Hujanen, T
显示头颈部鳞状细胞癌（HNSCC）的生物学侵袭性的有用标记物需要预测疾病的结果。MMP-2与几种实体癌的侵袭行为相关。在这项研究中，肿瘤组织和循环免疫反应蛋白MMP-2和TIMP-2的临床意义进行了评估。研究组包括74例HNSCC患者和44例健康对照。MMP-2和TIMP-2的表达在石蜡包埋的肿瘤切片通过免疫组织化学方法使用特异性抗体进行检测。采用ELISA法测定治疗前血清MMP-2、TIMP-2及MMP-2：TIMP-2复合物水平。并与临床病理因素及患者预后进行比较。MMP-2在肿瘤中的免疫组化过表达被发现是HNSCC中生存期缩短的预后因素，MMP-2在肿瘤中高阳性的患者的5年累积无复发生存率为42%，而MMP-2阴性或仅弱阳性的肿瘤患者的5年累积无复发生存率为61%（P = 0.045）。组织MMP-2阳性也与晚期淋巴结或造血复发密切相关，并与病因特异性生存率相关（P = 0.055）。同样，肿瘤TIMP-2免疫染色广泛阳性患者的5年病因特异性生存率显著低于TIMP-2阴性患者（40 vs 64%，P = 0.038）。TIMP-2阳性肿瘤患者的5年无复发生存率也很低（分别为43%和60%，P = 0.071）。此外，TIMP-2的过度表达是HNSCC中晚期淋巴结或血行转移的有力预测因子。血清MMP-2、TIMP-2或MMP-2：TIMP-2复合物水平与HNSCC的临床表现无关。本研究结果提供的证据表明，MMP-2和TIMP-2免疫反应蛋白在HNSCC患者的肿瘤组织中，但不是从术前血清样品测定时，是预后的估计侵袭性临床过程中的HNSCC。
Useful markers showing biological aggressiveness of head and neck squamous cell carcinoma (HNSCC) are needed to predict the outcome of the disease. MMP-2 is associated with aggressive behavior of several solid cancers. In this study, the clinical significance of tumor tissue and circulating immunoreactive proteins for MMP-2 and TIMP-2 was assessed in HNSCC. The study group consisted of 74 patients with HNSCC and 44 healthy controls. Expression of MMP-2 and TIMP-2 was examined in paraffin-embedded tumor sections by immunohistochemical methods using specific antibodies. The pretreatment serum levels of MMP-2, TIMP-2 and MMP-2: TIMP-2 complex were quantitatively measured by ELISA assay. The results were compared with the clinicopathological factors of the disease and the patients' outcome. Immunohistochemical overexpression of MMP-2 in tumor was found to be prognostic for shortened survival in HNSCC, the 5-year cumulative relapse-free survival being 42% in patients with high positivity for MMP-2 in tumor vs 61% in cases with a negative or only weakly MMP-2-positive tumor ( P = 0.045). Tissue MMP-2 positivity was also strongly connected with later lymph node or hematogenic relapses and associated to the cause-specific survival ( P = 0.055). Similarly, the 5-year cause-specific survival was significantly poorer in patients with extensive positive immunostaining for tumor TIMP-2 than in those with a TIMP-2-negative tumor ( 40 vs 64%, P = 0.038). Patients with a TIMP-2-positive tumor also had an unfavorable 5-year relapse-free survival rate ( 43 vs 60%, respectively, P = 0.071). Additionally, the overexpression of TIMP-2 was a powerful predictor of later lymph node or hematogenous metastases in HNSCC. Serum levels of MMP-2, TIMP-2 or MMP-2: TIMP-2 complex failed to associate with the clinical behavior of HNSCC in this material. The results of this study provide evidence that MMP-2 and TIMP-2 immunoreactive protein in tumor tissue of HNSCC patients, but not when assayed from preoperative serum samples, are prognostic in estimation of the aggressive clinical course of HNSCC.