Mast Cells are Responsible for Expression of α-Smooth Muscle Actin in Stromal Cells of the Uterine Cervix during Epithelial Neoplastic Changes

자궁경부상피의 악성변화에서 비만세포가 간질세포의 α-Smooth Muscle Actin 발현에 미치는 영향

There is increasing evidence that stromal reaction in cancer has an important diagnostic and prognostic significance. The aim of our study is to analyze the relation between the increase in mast cell number and the expression CD34 and alpha-smooth muscle actin (${\alpha}$-SMA) in the stroma of cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC). We investigated a total of 29 CIN (1,2,3) and 21 SCC (microinvasive and invasive) specimens and compared the distribution of $CD34^+$ stromal cells, ${\alpha}-SMA^+$ cells, transforming growth factor-${\beta}1$ $(TGF-{\beta}1)^+$ cells, and the density of mast cells using immunohistochemistry with antibodies against CD34, ${\alpha}$-SMA, TGF-${\beta}1$, and c-Kit (CD117) respectively. Computerized image analysis was to evaluate the positive area (%) and density of the respective immunoreactive cells. In CIN $CD34^+$ cells were abundant in the stroma but no ${\alpha}-SMA^+$ cells were identified except the wall of blood vessels. $CD34^+$ cells were progressively decreased along the continuum from CIN 2 to microinvasive SCC and not observed in the stroma of invasive SCC. Whereas ${\alpha}-SMA^+$ cells were only observed in the stroma of microinvasive and invasive SCC. We found more intense TGF-${\beta}1$ expression in the increased mast cells in the stroma of invasive SCCs than that in the stroma of CIN. These results indicate that disappearance of $CD34^+$ stromal cells and appearance of ${\alpha}-SMA^+$ cells are associated with the stromal change of CIN to SCC and the transformation of $CD34^+$ stromal cells into ${\alpha}-SMA^+$ cells is mediated by TGF-${\beta}1$ secretions in the stromal mast cell of SCC.