MMP2 expression is a prognostic marker for primary melanoma patients.
BACKGROUND
Matrix metalloproteinase 2 (MMP2) is a collagenase, which aids tumor growth and invasion by digesting the extracellular matrix surrounding the tumor tissue. Our study examined MMP2 expression in various stages of melanoma progression and tested the prognostic significance of MMP2 expression. We also analyzed the correlation between p-Akt status and MMP2 expression in melanoma patients.


METHODS
Tissue microarray (TMA) and immunohistochemistry were employed to study the expression of MMP2. A total of 482 melanoma (330 primary and 152 metastatic) tumor biopsies and 149 nevi biopsies (49 normal and 100 dysplastic nevi) were used for the analysis. MMP2 expression was correlated with melanoma progression. Kaplan-Meier survival curve and multivariate Cox regression analysis were applied to verify the prognostic significance of MMP2 expression. The correlation between MMP2 and p-Akt expression was analyzed in 92 cases which were common in the present and the previous study on p-Akt expression.


RESULTS
Strong MMP2 expression is significantly increased in primary (25 %) and metastatic melanoma (43 %) compared to normal (5 %) and dysplastic nevi (10 %). Patients with strong MMP2 had significantly poorer survival compared to those with negative-to-moderate MMP2 expression. MMP2 expression could predict the patient survival independent of tumor thickness and ulceration. Furthermore, in our cohort study MMP2 expression was associated with p-Akt status and patient survival.


CONCLUSIONS
Strong MMP2 staining is associated with worse survival of melanoma patients and is an independent molecular prognostic factor for primary melanoma.
Department of Dermatology and Skin Science, Jack Bell Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada.
Anand
A
Rotte
Magdalena
M
Martinka
Gang
G
Li
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
D014408:Biomarkers, Tumor; D051057:Proto-Oncogene Proteins c-akt; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2