Expression of matrix metalloproteinase-1, -9, -13, and tissue inhibitor of metalloproteinases-1 in basal cell carcinomas of the eyelid.

BACKGROUND

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) function in the remodelling of the extracellular matrix in morphogenesis, angiogenesis, tissue repair, and tumor invasion. Elevated levels of distinct MMPs in tumor tissue are related to worse prognosis. However, no overall consistent pattern of expression in human cancer has been identified. The aim of the present study was to evaluate the expression of MMP-1, -9, -13 and TIMP-1 in tumor epithelial cells and surrounding connective tissue in primary basal cell carcinomas (BCC) of the eyelid, and to assess their role as prognostic markers for tumor recurrence.

METHODS

Surgical specimens of 49 histologically proven primary BBCs of the eyelid of different histological subtypes were included. Immunohistological studies were performed using antibodies against MMP-1, MMP-9, MMP-13 and TIMP-1, and staining intensity was analyzed semi-quantitatively.

RESULTS

MMP-1, -9, -13, and TIMP-1 were expressed at various intensities in epithelial tumor cells and surrounding stromal cells including fibroblasts, inflammatory cells, and vascular endothelial cells in all tumor subtypes. Staining was especially prominent at the invading edge of the BCC. A statistically significant correlation was seen between increased TIMP-1 expression in tumor and/or stromal cells with the presence of MMP-13 (p = 0.007 and p < 0.0001 respectively). Moreover, TIMP-1 expression in tumor and/or stroma was significantly associated with relapse (p = 0.012 and p = 0.042 respectively).

CONCLUSION

MMP-9, MMP-13 and TIMP-1 expression may serve as a prognostic marker for early tumor invasiveness. Moreover, up-regulation of TIMP-1 in tumor and/or surrounding stromal cells may indicate an increased risk for BCC recurrence.