Keratinocyte growth factor colocalized with perlecan at the site of capsular invasion and vascular involvement in salivary pleomorphic adenomas

Abstract

Capsular invasion is often observed in daily pathologic diagnosis of pleomorphic adenomas, although neither actual information about its occurrence nor molecular mechanisms leading to their invasive activities have been reported. In this study, our aim was to elucidate the mode and the frequency of capsular invasion in this tumor and to characterize the tumor cell arrangement at the site of capsular invasion. The mode and frequency of capsular invasion of salivary pleomorphic adenomas were histopathologically examined in 104 surgical specimens of pleomorphic adenoma, and stromal characteristics, and tumor cell arrangements at the sites of capsular invasion were immunohistochemically investigated. A total of 353 areas with capsular invasive changes were collected from 104 cases. The mode of capsular invasion was classified into two types: type I: intracapsular invasion (247 areas, 70%) and type II: capsular penetration (106 areas, 30%). Myxoid stroma, which was perlecan-immunopositive (+), was shared by both type I and type II sites, while tumor cell foci containing ductal structures were predominant in type II sites. These foci were composed of KGF(+) and FGFR2(+) cells. In addition, apparent vascular involvement was recognized in 31 tumors (29.8%). The results suggest that pleomorphic adenoma cells are able to invade into the capsule and involve blood vessels when they are situated in perlecan-rich milieu, which accelerate KGF signaling.