Metaloproteinases 2 e 9: expressão, inibidores teciduais e inibição por extratos naturais no carcinoma de células basais e carcinoma espinocelular

Abstract

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin are locally agressive malignant neoplasms. Matrix metalloproteinasis (MMP) have been strongly implied in the tumoral progression since these enzymes interfere with invasive and angiogenic properties. On the other hand, tissue inhibitors of MMP (TIMP) may posses biologic properties enrolled in suppression of neoplastic growth. The aims of the present work were 1. to identify the expression of MMP-2 and -9, and TIMP-1 and -2 in samples of BCC and SCC by immunohistochemistry; 2. to evaluate possible associations between the immunoexpression of MMP / TIMP and clinicopathologic parameters of BCC and SCC; and 3. to access the gelatinolitic activity of homogentisates obtained from fresh samples of BCC and, in addition, to verify the inhibitory properties over this activity of infusions prepared with black tea, Aloe vera, or Annona muricata. The immunostaining of MMP was usually stronger than that of TIMP. Strong staining was more frequent for all of the studied enzymes in the adjacent non-neoplastic epithelium than in the neoplasms. In BCC, indices of positiveimmunostaining of neoplastic cells were 43.7% (±30.4%) for MMP-2, 78.8% (± 8.3%) for MMP-9, 82.5% (± 5.5%) for TIMP-1, and 71.2% (±9.0%) for TIMP-2. In SCC, these indices were 82.8% (±5.5%) for MMP-2, 96.2% (±1.7%) for MMP-9, 93.7% (±4.2%) for TIMP-1, and 82.7% (±8.5%) for TIMP-2. There were not significant correlations between immunostaining indices of these enzymes, except for a positive correlation between MMP-9 and TIMP-1 for SCC. In the same way, there were notsignificant associations between these indices and clinicopathologic features of the lesions. In SCC, there were significant differences between immunostaining indices of MMP-2 versus MMP-9, TIMP-1 or TIMP-2; between MMP-9 versus TIMP-2; and between TIMP-1 versus TIMP-2. The gelatinolitic activity of MMP was significantly inhibited by aqueous extracts of Aloe vera and black tea, and Annona muricata. Inconclusion, the expression of MMP and TIMP do not evidently influence the biological behavior of the present cases. The concomitant expression of these enzymes suggests equilibrium between them in both BCC and SCC. Additional investigation is required to better understand the influence of degradative roles of MMP in these malignant lesions.The inhibition of the gelatinolitic activity of MMP by extracts of Aloe vera and black tea seems to indicate interesting antineoplastic properties for these plants.