Immunohistochemical characterization of mullerian mucinous borderline tumors: possible histogenetic link with serous borderline tumors and low-grade endometrioid tumors.

Mullerian mucinous borderline tumor and gastrointestinal mucinous borderline tumor are considered mucinous tumor subtypes. However, it has been reported that mullerian mucinous borderline tumor shares many clinicopathologic features with serous borderline tumor. Furthermore, some investigators have explained the histogenesis of mullerian mucinous borderline tumor by metaplastic and hyperplastic transformation of endometriosis (Fukunaga M, Ushigome S. Epithelial metaplastic changes in ovarian endometriosis. Mod Pathol. 1998;11:784-788). The purpose of this study is to substantiate the concept that mullerian mucinous borderline tumor is histogenetically closer to serous borderline tumor or low-grade endometrioid tumor than to gastrointestinal mucinous borderline tumor by directly comparing their immunophenotype. A total of 80 cases of low-grade ovarian tumors composed of 20 mullerian mucinous borderline tumors, 20 gastrointestinal mucinous borderline tumors, 20 serous borderline tumors, and 20 low-grade endometrioid tumors were immunohistochemically evaluated for the expression of estrogen receptor, progesterone receptor, vimentin, WT-1, beta-catenin, and PTEN. Almost all cases of mullerian mucinous borderline tumor, serous borderline tumor, and low-grade endometrioid tumor showed diffuse and strong nuclear expression of estrogen receptor and progesterone receptor. In addition, about half of the mullerian mucinous borderline tumor, serous borderline tumor, and low-grade endometrioid tumor cases showed focal but strong vimentin cytoplasmic expression. In contrast, gastrointestinal mucinous borderline tumor showed no expression of estrogen receptor, progesterone receptor, or vimentin, except for 1 case in which estrogen receptor expression was very focally and weakly observed. WT-1 nuclear expression was observed in most serous borderline tumors and only 15% of low-grade endometrioid tumor, but mullerian and gastrointestinal mucinous borderline tumor cases were completely negative. beta-Catenin nuclear expression was significantly more frequent in low-grade endometrioid tumor than in mullerian mucinous borderline tumor, gastrointestinal mucinous borderline tumor, or serous borderline tumor. PTEN expression was significantly lower in low-grade endometrioid tumor than in mullerian mucinous borderline tumor, gastrointestinal mucinous borderline tumor, and serous borderline tumor. Multiple comparisons of quantitative immunoreactivities of estrogen receptor, progesterone receptor, and vimentin revealed that the gastrointestinal mucinous borderline tumor expression profiles were significantly different from those of mullerian mucinous borderline tumors, serous borderline tumors, and low-grade endometrioid tumors. The immunohistochemical expression profiles of estrogen receptor, progesterone receptor, and vimentin substantiate the concept that the histogenesis of mullerian mucinous borderline tumor is closer to those of serous borderline tumor and low-grade endometrioid tumor than to that of gastrointestinal mucinous borderline tumor. However, aberrant beta-catenin and PTEN protein expression, both of which are known to contribute to the tumorigenesis of low-grade endometrioid tumor, appeared to be less important for the tumorigenesis of mullerian mucinous borderline tumor.