Expression of VCAN and its receptors in canine mammary carcinomas with or without myoepithelial proliferation

The proteoglycan versican (VCAN) plays a complex role in cancer. The expression of this molecule has been related to invasion and progression in malignant mixed tumors, such as carcinoma in mixed tumors (CMT) of the canine mammary gland. In addition, its interaction with surface cell receptors EGFR, HER-2 and CD44 in malignant epithelial cells may be responsible for proliferation and cellular motility in early stages of cancer. We comparatively evaluated the expression of this proteoglycan and its receptors in in situ and invasive areas of simple carcinomas (SC) and CMT to investigate similarities and differences between these histological types. Immunohistochemistry was performed with anti-VCAN, anti-CD44, anti-EGFR and anti-HER-2 antibodies in 32 cases of SC or CMT. VCAN was highly expressed in stroma adjacent to invasive areas in SC and CMT. CMTs presented comparatively higher expression of VCAN in stroma adjacent to in situ and in invasive areas than in corresponding areas in SCs. In CMT, EGFR and HER-2 expressions were higher in situ compared to invasive areas. In contrast, increased CD44 and EGFR expression was found in invasive areas in SC compared to CMT. These results indicate that versican expression is similarly associated with invasiveness in SC and CMT, however higher levels were seen in CMT suggesting that the presence of myoepithelial proliferation in this tumor type participates in stromal composition and promoting an increase in the expression of versican.