Our objective was to evaluate the relationship between MMP-9 and EGFR expression in non-small cell lung cancer (NSCLC) and to assess the impact of expression on clinicopathological parameters and survival.

This is a retrospective study of 169 patients who underwent resection for stage I-IIIa NSCLC with a postoperative survival >60 days, Minimum follow-up was 2 years. Standard avidin-biotin complex immunohistochemistry was performed on 4-mu m paraffin-embedded sections from the tumor periphery using monoclonal antibodies to EGFR and MMP-9.

MMP-9 was expressed in the tumor cells of 88 of 169 (52%) cases, EGFR expression was found in 94 of 169 (56%) cases [membranous, 55 of 169 (33%); cytoplasmic, 39 of 169 Stroma (23%). MMP-9 expression was associated with poor out-come in univariate (P = 0.0023) and multivariate (P = 0.027) analysis. Membranous, cytoplasmic, and overall EGPR expression were not associated with outcome (P = 0.13, 0.99, and 0.17, respectively). MMP-9 expression showed a strong correlation with EGFR expression (P < 0.0001) and EGFR membranous expression (P = 0.002) but not with cytoplasmic EGFR expression (P = 0.18), Coexpression of MMP-9 and EGPR (37%) conferred a worse prognosis (P = 0.0001). Subset analysis revealed only MMP-9 and membranous EGFR co-expression (22%) was associated with poor outcome (P = 0.0019).

Our results show that a significant proportion of NSCLC tumors co-express MMP-9 and EGFR. The coexpression of these markers confers a poor prognosis. This finding suggests that EGFR signaling pathway may play an important role in the invasive behavior of NSCLC via specific up-regulation of MMP-9.