Miyazaki T, Kato H, Nakajima M, Faried A, Takita J, Sohda M, Fukai Y, Yamaguchi S, Masuda N, Manda R, Fukuchi M, Ojima H, Tsukada K, Kuwano H
Department of General Surgical Science (Surgery I), Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan.
Br J Cancer. 2004 Oct 18;91(8):1556-60. doi: 10.1038/sj.bjc.6602185.
Tissue inhibitor of metalloproteinase-3 (TIMP-3) inhibits the activity of matrix metalloproteinase, which may play an important role in carcinoma invasion and metastasis. We have investigated the relationship between TIMP-3 reduction and clinicopathological factors in oesophageal squamous cell carcinoma (ESCC). We examined tissue specimens that had been removed from 90 patients with thoracic oesophageal cancer who had undergone surgery between 1983 and 2001. Immunohistochemical staining was performed by the standard streptavidin-biotin method. Immunostaining of TIMP-3 was seen in the cytoplasm of cancer cells and normal oesophageal epithelial cells, particularly in cells located in shallow areas of the tumour. TIMP-3 preserved (+), moderate (+/-), and reduced (-) cases accounted for 30, 27, and 33 of the 90 patients, respectively (33, 30, 37%). Significant correlations were observed between TIMP-3 expression and depth of tumour invasion (P=0.001), number of lymph node metastases (P=0.003), infiltrative growth pattern (P=0.003), and disease stage (P=0.005). The survival rates of patients with TIMP-3 (-) cancer were significantly lower than those of patients with TIMP-3 (+) and TIMP-3 (+/-) cancer (P=0.0003). The mean 5-year survival rates of patients with TIMP-3 (+), (+/-), and (-) were 50, 58, and 21%, respectively. In conclusion, decreased expression of TIMP-3 protein correlates with invasive activity and metastasis. This makes the prognosis for patients with cancer that has lost TIMP-3 significantly less favourable than that for patients with cancer that has maintained TIMP-3.
金属蛋白酶组织抑制剂-3（TIMP-3）可抑制基质金属蛋白酶的活性，这可能在癌侵袭和转移中起重要作用。我们研究了TIMP-3降低与食管鳞状细胞癌（ESCC）临床病理因素之间的关系。我们检查了1983年至2001年间接受手术的90例胸段食管癌患者切除的组织标本。采用标准链霉亲和素-生物素法进行免疫组织化学染色。TIMP-3免疫染色见于癌细胞和正常食管上皮细胞的细胞质中，尤其是位于肿瘤浅表区域的细胞。TIMP-3保存（+）、中度（+/-）和降低（-）的病例分别占90例患者中的30、27和33例（33%、30%、37%）。观察到TIMP-3表达与肿瘤浸润深度（P=0.001）、淋巴结转移数量（P=0.003）、浸润性生长模式（P=0.003）和疾病分期（P=0.005）之间存在显著相关性。TIMP-3（-）癌患者的生存率显著低于TIMP-3（+）和TIMP-3（+/-）癌患者（P=0.0003）。TIMP-3（+）、（+/-）和（-）患者的平均5年生存率分别为50%、58%和21%。总之，TIMP-3蛋白表达降低与侵袭活性和转移相关。这使得失去TIMP-3的癌症患者的预后明显不如维持TIMP-3的癌症患者。
