Matrix metalloproteinase-1 is differentially expressed in signet ring cell, and intestinal colorectal carcinomas histotypes

Abstract

14564 Background: Signet ring cell colorectal carcinoma ( SRCC) pure is an infrequent and highly malignant variant of colorectal cancer, while this histological component is present in 30% of all colorectal carcinomas. In our previous studies we compared the E- Cadherin, β- Catenin, Fibronectin, Ki 67 and Thymidylate Synthase (TS) expression of SRCC, the intestinal type of colorectal carcinoma (ICRC) to try to explain the pathogenesis, the aggressiveness and the low 5 Fluorouracil (5FU) responsiveness of these tumours. We found that all SRCCs had very low levels of all markers and were in the post- mitotic phase of the cell cycle. To understand their high metastatic capability we assessed the SRCC expression of Matrix Metallo Proteinase-1 (MMP1), a proteolytic enzyme, suspected to play an important role in the progression of various cancer and compared it to the ICRC one. Methods: We tested MMP1 expression immunohistochemically on formalin-fixed, paraffin-embedded samples of 32 SRCC and 70 ICRC. Differences in the distribution of the study variables, and associations between variables were assessed by means of the ?2 test. Results: SRCC showed a high expression of MMP1 over all in the invasion front of the tumour and in the neoplastic embolus rather then the ICRC (p<0.001). Conclusions: As MMPs seem to play important role in tumour invasion and metastasis, recently they have gained attention as targets for new anticancer therapy strategies. MMPs inhibitors have been shown to prevent tumour spread both in vitro and in vivo and to inhibit tumour angiogenesis and some of them are being developed for clinical use. In these study we demonstrated that SRCCs showed a different MMP1 expression pattern from the ICRC one, for this reason an anti-MMP therapy should be advisable in these patients, because of their bad prognosis. No significant financial relationships to disclose.