Itoh Fumio, Imai Kohzo
First Department of Internal Medicine, Sapporo Medical University, Sapporo 060-8543.
Rinsho Byori. 2003 Feb;51(2):158-67.
Matrix metalloproteinases have been implicated in tumor progression. Matrilysin is one of the matrix metalloproteinases and is frequently overexpressed in gastrointestinal cancers. The aim of this study was to assess the validity of matrilysin as a prognostic marker of colorectal cancers. Matrilysin expression was immunohistochemically analyzed using formalin-fixed, paraffin-embedded specimens from 113 colorectal cancer patients who had undergone curative surgery. The lumenal surface of neoplastic glands in the superficial layer was apically stained, while the cytoplasm of cancer cells at the invasive front was diffusely stained for matrilysin. Sections with immunostaining signals in more than 30% of carcinoma cells at the invasive front, which were observed in 47(42%) cases, were judged as being positive for matrilysin. Matrilysin positivity was significantly correlated with the depth of invasion, lymph node metastasis, lymphatic invasion, advanced Dukes' stage, and poor outcome. Patients with matrilysin-positive cancer had a significantly shorter overall survival time than those with matrilysin-negative cancer. For patients with intermediate invasive tumor(T2 or T3), only matrilysin was a significant prognostic variable for predicting overall survival in multivariate analysis. Matrilysin expression at the invasive front could be an important marker, predicting an unfavorable prognosis after surgical treatment in patients with colorectal cancer.
基质金属蛋白酶与肿瘤进展有关。基质溶素是基质金属蛋白酶之一，在胃肠道癌症中经常过度表达。本研究的目的是评估基质溶素作为结直肠癌预后标志物的有效性。使用来自113例接受根治性手术的结直肠癌患者的福尔马林固定、石蜡包埋标本进行免疫组织化学分析基质溶素表达。表层肿瘤腺体的管腔表面呈顶端染色，而侵袭前沿癌细胞的细胞质中基质溶素呈弥漫性染色。在47例（42%）病例中观察到侵袭前沿超过30%的癌细胞有免疫染色信号的切片被判定为基质溶素阳性。基质溶素阳性与侵袭深度、淋巴结转移、淋巴管侵袭、Dukes分期晚期及不良预后显著相关。基质溶素阳性癌症患者的总生存时间明显短于基质溶素阴性癌症患者。对于中度侵袭性肿瘤（T2或T3）患者，在多变量分析中，只有基质溶素是预测总生存的重要预后变量。侵袭前沿的基质溶素表达可能是一个重要标志物，可预测结直肠癌患者手术治疗后的不良预后。
