Extracellular matrix
metalloproteinase (
MMP) inducer (
EMMPRIN, CD147) is a multifunctional
protein that has been implicated in
cancer invasion and
metastasis by the induction of
MMPs. To address its role in primary
tumors of human
non-small-cell lung cancer we assessed whether
EMMPRIN expression is associated with the expression of MMP-2 and MMP-9 and with patient survival. Primary
tumors of 150 patients (65
adenocarcinomas, 58
squamous cell carcinomas, and 27 of other subtypes) with completely resected
lung cancers were stained by immunohistochemistry. We assessed intensity, extent, and cellular localization of
EMMPRIN staining and determined MMP-2 and MMP-9 expression. 145
tumors expressed
EMMPRIN (strong expression in 61
tumors), which was predominantly localized at the
tumor cell membranes in 102 (68%) patients. We could not determine any correlation between
EMMPRIN expression and MMP-2 or MMP-9 expression. The prognostic relevance of
EMMPRIN was evaluated by Kaplan-Meier and multivariate Cox regression analysis in patients with
adenocarcinoma (n=57) and
squamous cell carcinoma of the lung (n=56). The median follow-up period was 36.0 months (range 4-156 months). Staining scores for
EMMPRIN and MMP-2 and MMP-9 derived from staining intensities and percentages of positive cells did not predict outcome of patients. In contrast, univariate survival analysis demonstrated that membranous localization of
EMMPRIN was associated with shortened survival in patients with
adenocarcinoma (P=0.03; log-rank test), but not in
squamous cell carcinoma. For the former patients, membranous
EMMPRIN expression was also an independent predictor of patient survival (P=0.04; Cox regression analysis). The findings point to a role of
EMMPRIN for the progression of
adenocarcinoma of the lung that is unrelated to its function as inducer of
MMPs.