Evaluation of the association of matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-2 (MMP-2) expression with KRAS and BRAF mutational status or survival outcomes in colorectal cancer (CRC) patients.

Abstract

452 Background: MMP-1 and MMP-2 proteins are felt to be involved in tumor growth, invasion and metastasis and may be regulated by the KRAS pathway. Methods: A tissue microarray was constructed from archival formalin-fixed paraffin-embedded primary tumor tissue samples of 96 patients with metastatic CRC. MMP-1 and MMP-2 expression was measured semiquantitatively by immunohistochemistry and graded 0 to 2. Mutation analysis was done for KRAS in codons 12 and 13, and patients without KRAS mutations were tested for BRAF V600E mutation. Chi-squared test, Fisher's exact test and Cox-proportionate hazard ratios were used for statistical analysis. Results: 96 patients had samples available for analysis (median age at diagnosis 60, 57% male, 46% stage IV at diagnosis, 33/93 (35%) KRAS mutated, 7/51 (14%) BRAF mutated, 22% received anti-EGFR therapy). No significant association was identified between MMP-1 and KRAS (p=0.88) or BRAF (p=0.54), or between MMP-2 and KRAS (p=0.08) or BRAF (p=0.41). Neither overall survival nor survival from diagnosis of metastatic disease were affected by MMP-1 or MMP-2 expression. Conclusions: MMP-1 and MMP-2 expression is not associated with KRAS or BRAF mutational status and is not a prognostic factor in our cohort of CRC patients. No significant financial relationships to disclose.