Increased immunoreactivity of membrane type-1 matrix metalloproteinase (MT1-MMP) and β-catenin in high-risk basal cell carcinoma.

Abstract

Although various immunohistological markers have been investigated to assess the aggressive characteristics of basal cell carcinoma (BCC), the role of membrane type-1 matrix metalloproteinase (MT1-MMP) has not been well established. To clarify the precise role of MT1-MMP in BCC, MT1-MMP expression was studied in various histological subtypes of BCC. High-risk subtypes of BCC were compared by assessing the expression of β-catenin and MT1-MMP. The tissue microarray technique was used for immunohistochemical staining. Fifty-eight samples were divided into six subtypes (10 nodular, 12 mixed, nine infiltrative, eight morphoeiform, 10 micro-nodular and nine basosquamous). Overall, the 10 nodular BCC samples were classified as low-risk BCC and the remaining 48 samples were classified as high-risk BCCs. β-Catenin immunoreactivity was increased in the high-risk BCCs compared with the low-risk (nodular) BCC (P < 0·001). Nuclear β-catenin immunoreactivity was increased at the invading front of mixed BCC tumour islands compared with the upper portion of the lesion (P < 0·01). For the mixed BCC (P < 0·01), infiltrative BCC (P < 0·001), morphoeiform BCC (P < 0·001), micronodular BCC (P < 0·001) and basosquamous (P < 0·001) carcinoma, β-catenin immunoreactivity was increased at the invading front compared with nodular BCC. MT1-MMP immunoreactivity was increased in the high-risk BCCs compared with the low-risk (nodular) BCC (P < 0·01). The membranous MT1-MMP immunoreactivity was increased at the invading front of mixed BCC tumour islands compared with the upper portion of the lesions (P < 0·01). For the mixed (P < 0·01), infiltrative (P < 0·05), morphoeiform (P < 0·05), micronodular (P > 0·05) and basosquamous (P < 0·05) BCC, MT1-MMP immunoreactivity was also increased at the invading front compared with nodular BCC. The results of this study suggest that MT1-MMP might be a novel marker for high-risk BCC. In addition, expression of both β-catenin and MT1-MMP was increased in high-risk BCC tumour cells, indicating that these two proteins may play an important role in locally invasive and highly destructive growth behaviour of high-risk BCCs.