The increase in tryptase- and chymase-positive mast cells is associated with partial inactivation of chymase and increase in protease inhibitors in basal cell carcinoma

J Eur Acad Dermatol Venereol. 2007 Aug;21(7):908-15. doi: 10.1111/j.1468-3083.2006.02100.x.

Abstract

Background: In basal cell carcinoma (BCC), mast cells accumulate in the peritumoral stroma. The serine proteinases tryptase and chymase are the major mediators in mast cell granules and they may exert their enzymatic activity in the BCC lesion by inducing matrix remodeling and epithelial cell detachment.

Objective: To analyse the numbers of mast cells showing tryptase enzyme activity, chymase enzyme activity and chymase immunoreactivity as well as the presence of chymase inhibitors alpha(1)-antichymotrypsin (alpha(1)-AC), alpha(1)-proteinase inhibitor (alpha(1)-PI) and squamous cell carcinoma antigen-2 (SCCA-2) in BCC.

Methods: Eleven biopsies were taken from the lesion and healthy-looking skin of 10 patients with superficial spreading BCC. The frozen biopsies were analysed enzyme- and immunohistochemically, and a sequential double-staining method was applied.

Results: In the BCC lesion, the number of mast cells with tryptase activity and chymase immunoreactivity was significantly increased by 2.2- to 2.3-fold. Practically all tryptase-immunopositive cells contained tryptase activity although occasional tryptase-immunopositive cells (about 1% of total) revealed no activity. However, the ratio of cells with chymase activity to those with chymase immunoreactivity was significantly decreased from 49 +/- 19% in the healthy skin to 33 +/- 19% in the BCC lesion. Instead, the percentage of mast cells displaying alpha(1)-AC or alpha(1)-PI immunoreactivity was significantly increased by 1.7-fold in the BCC lesion. SCCA-2 expression was strongly increased in the malignant BCC epithelium but mostly in the suprabasal layers.

Conclusions: Tryptase- and chymase-positive mast cells (MC(TC)) increased in the BCC lesion. However, chymase is partially inactivated, possibly by the effective chymase inhibitors alpha(1)-AC and alpha(1)-PI. SCCA-2 increased in BCC, but was localized mostly to the suprabasal layers, and thus it seems not to be crucial in inhibiting chymase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biopsy
  • Carcinoma, Basal Cell / enzymology*
  • Chymases / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Male
  • Mast Cells / enzymology*
  • Middle Aged
  • Protease Inhibitors / metabolism*
  • Skin Neoplasms / enzymology*
  • Tryptases / metabolism*

Substances

  • Protease Inhibitors
  • Chymases
  • Tryptases