Increased Chymase-Positive Mast Cells in High-Grade Mucoepidermoid Carcinoma of the Parotid Gland

Abstract

It has long been known that high-grade mucoepidermoid carcinoma (MEC) has a poor prognosis, but the detailed molecular and biological mechanisms underlying this are not fully understood. In the present study, the pattern of chymase-positive mast cells, as well as chymase gene expression, in high-grade MEC was compared to that of low-grade and intermediate-grade MEC by using 44 resected tumor samples of MEC of the parotid gland. Chymase expression, as well as chymase-positive mast cells, was found to be markedly increased in high-grade MEC. Significant increases in PCNA-positive cells and VEGF gene expression, as well as lymphangiogenesis, were also confirmed in high-grade MEC. Chymase substrates, such as the latent transforming growth factor-beta (TGF-β) 1 and pro-matrix metalloproteinase (MMP)-9, were also detected immunohistologically in high-grade MEC. These findings suggested that the increased chymase activity may increase proliferative activity, as well as metastasis in the malignant condition, and the inhibition of chymase may be a strategy to improve the poor prognosis of high-grade MEC of the parotid gland.

Keywords: angiotensin II; chymase; mast cell; mucoepidermoid carcinoma; salivary glands.

Figure 1

Representative HE and Azan Mallory staining in the cross-sections from the I–L and H groups. Black hashes indicate cystic lesions and black asterisks indicate solid tumor tissues.

Figure 2

Representative vimentin and α-SMA immunostaining in the serial cross-sections from the I–L and H groups. The yellow frames of the vimentin and α-SMA immunostaining correspond to the positions of the yellow frames of Azan-Mallory staining.

Figure 3

Representative toluidine blue staining, as well as the calculated number of mast cells in the I–L and H groups. Red arrows indicate mast cells. As can be seen in these photographs, the cytoplasm of mast cells is stained purple with toluidine blue.

Figure 4

Representative chymase immunostaining and the calculated number of chymase-positive cells, as well as chymase gene expression in the I–L and H groups. Navy blue arrows indicate chymase-positive cells.

Figure 5

Representative tryptase immunostaining and the calculated number of tryptase-positive cells, as well as tryptase gene expression in the I–L and H groups. Navy blue arrows indicate tryptase-positive cells.

Figure 6

Representative toluidine blue, chymase, and tryptase staining in the serial cross-sections positioned before and after toluidine blue staining. Yellow arrows indicate mast cells, chymase-positive, and tryptase-positive cells, respectively. Mast cells confirmed by toluidine blue staining are almost in the same position as the chymase-positive and tryptase-positive cells (HPF 1000×), indicating that mast cells are the main cellular source in these tumors.

Figure 7

Representative PCNA immunostaining, as well as the estimated numbers of PCNA-positive cells in the I–L and H groups.

Figure 8

Representative podoplanin and vWF immunostaining, as well as gene expression levels of VEGF in the I–L and H groups. Navy blue and green arrows indicate lymphatics and blood vessels, respectively.

Figure 9

Representative HE and Azan Mallory staining from the H group. The images of MMP-9, MMP-2, TGFβ1, and SCF immunostaining are also serial cross-sections from the same individual.