Role of e-cadherin, α-, β-, and γ-catenins, and p120 (Cell adhesion molecules) in prolactinoma behavior

Abstract

E-cadherin/catenin complex regulates cellular adhesion and motility and is believed to function as an invasion suppressor system. In a number of cancers, abnormal and reduced expression of E-cadherin/catenin complex is associated with tumor invasion and metastasis. Prolactinomas show frequent invasion on the surrounding structures, despite their histologically benign nature. Furthermore, gender-based differences in endocrine and surgical findings are found in patients with prolactinoma. To understand biological factors governing prolactinoma behavior, this study analyzed the expression of E-cadherin; α-, β-, and γ-catenins; p120; and cell proliferation marker MIB-1 labeling index in 13 invasive tumors (9 in men, 4 in women), 26 noninvasive tumors (4 in men, 22 in women), and 8 normal anterior pituitaries by immunohistochemistry. Immunostaining of E-cadherin; β-, β-, and γ-catenins; and p120 showed a membranous pattern of reactivity and generally stronger in normal pituitaries than in prolactinomas. Expression of E-cadherin and β-catenin was significantly lower in invasive than in noninvasive prolactinomas (P < .002 and P < .005, respectively), and reduced expression of E-cadherin and β-catenin was more frequent in invasive than in noninvasive prolactinomas (P < .001 and P < .05, respectively); in contrast, γ-catenin expression showed higher in invasive than in noninvasive prolactinomas (P < .05). Expression of E-cadherin was significantly lower in macroprolactinomas than in microprolactinomas (P < .01), and decreased expression of E-cadherin and β-catenin predicted high MIB-1 expression (P < .05). Moreover, the expression of E-cadherin and β-catenin was significantly lower in macroprolactinomas in men than in those in women (P < .01 and P < .02, respectively). No statistical correlations were observed between expression of α-catenin, p120, and clinicopathologic features. In conclusion, the reduction of E-cadherin and β-catenin expression was related to invasiveness and proliferative status of prolactinomas and correlated with the more aggressive behavior of prolactinomas in men compared with in women.