Expression of matrix metalloproteinase-1 in human colorectal carcinoma

Matrix metalloproteinases are considered to play an important role in tumor invasion and metastasis, To elucidate the involvement of MMP-1 in human co lorectal carcinoma, we performed immunohistochemical analysis on tissues fr om 20 colorectal adenomas and 142 colorectal adenocarcinomas, including 27 intramucosal carcinomas and 115 invasive carcinomas. MMP-1 was not expresse d in any of the 20 cases of colorectal adenoma examined. In contrast, 108 o f 142 cases (76.1%) with colorectal adenocarcinoma showed immunoreactivity for MMP-1 in the carcinoma cells themselves. Expression of MMP-1 was also i dentified in stromal cells around the carcinoma. We investigated the relati onship between pathological features in colorectal carcinoma and MMP-1 immu noreactivity of the tumor cells. MMP-1 expression was less frequent in intr amucosal carcinomas and weaker than that in invasive carcinomas (P <.0001), Among the 115 cases of invasive carcinomas, MMP-1 immunoreactivity was sig nificantly correlated with the depth grading of tumor invasion (P <.05), tu mor growth pattern (P <.05), the presence of lymphatic invasion (P <.05), v enous invasion (P <.05), neural invasion (P <.05), lymph node metastasis (P <.005), hepatic metastasis (P <.05), and increasing stages of Dukes' class ification (P <.05). In situ hybridization, using an MMP-1 oligonucleotide p robe, confirmed the presence of MMP-1 mRNA in colorectal carcinoma cells th emselves. Expression of MMP-1 mRNA was detected by the reverse transcriptio n polymerase chain reaction method in cultured human colorectal carcinoma c ell Lines and colon carcinoma tissue obtained at surgery. These findings su ggest that the expression of MMP-1 is one of the important factors related to tumor invasion and metastasis in colorectal carcinoma.