Matrix metalloproteinases are considered to play an important role in tumor invasion and metastasis. To elucidate the involvement of MMP-1 in human colorectal carcinoma, we performed immunohistochemical analysis on tissues from 20 colorectal adenomas and 142 colorectal adenocarcinomas, including 27 intramucosal carcinomas and 115 invasive carcinomas. MMP-1 was not expressed in any of the 20 cases of colorectal adenoma examined. In contrast, 108 of 142 cases (76.1%) with colorectal adenocarcinoma showed immunoreactivity for MMP-1 in the carcinoma cells themselves. Expression of MMP-1 was also identified in stromal cells around the carcinoma. We investigated the relationship between pathological features in colorectal carcinoma and MMP-1 immunoreactivity of the tumor cells. MMP-1 expression was less frequent in intramucosal carcinomas and weaker than that in invasive carcinomas (P < .0001). Among the 115 cases of invasive carcinomas, MMP-1 immunoreactivity was significantly correlated with the depth grading of tumor invasion (P < .05), tumor growth pattern (P < .05), the presence of lymphatic invasion (P < .05), venous invasion (P < .05), neural invasion (P < .05), lymph node metastasis (P < .005), hepatic metastasis (P < .05), and increasing stages of Dukes' classification (P < .05). In situ hybridization, using an MMP-1 oligonucleotide probe, Colorectal carcinoma is the most common malignant tumor of the alimentary tract in the Western world. At the time of diagnosis, colorectal carcinoma usually shows extensive local invasion and metastasis. Enzymatic degradation of the extracellular matrix, such as basement membrane and interstitial stroma, is an essential step in tumor invasion and metastasis (1). Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent enzymes that are involved in the degradation of the extracellular matrix (2). According to their structures and substrate specificities, MMPs can be classified into subgroups of collagenases (MMP-1, MMP-8, and MMP-13), gelatinases (MMP-2 and MMP-9), stromelysins (MMP-3, MMP-10, MMP-12, and MMP-7), membrane-type MMPs (MT-MMPs) and other MMPs. Currently, this family of MMPs has at least 17 different members (3). Tumor invasion is facilitated by degradation of the interstitial stroma, which is the main component of the extracellular matrix. This process can be furthered by collagenases, particularly interstitial collagenase (MMP-1) (4). A requirement for MMP-1 for tumor invasion has been demonstrated in in vitro assays (5). However, the tissue distribution and the role of MMP-1 in vivo are still controversial. Previously, MMP-1 was shown to be expressed mainly in stromal cells surrounding the carcinoma cells (6 -9). In contrast, recent studies have reported MMP-1 expression by the carcinoma cells themselves and suggested a relationship between tumor progression and this MMP-1 expression (10 -13). Murray et al. (11) have described that immunohistochemically detected MMP-1 expression by the tumor cells was associated with poor prognosis of patients w...