title: Role of E-cadherin, alpha-, beta-, and gamma-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; alpha-, beta-, and gamma-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; alpha-, beta-, and gamma-catenins; and p120 showed a membranous pattern of reactivity and generally stronger in normal pituitaries than in prolactinomas. Expression of E-cadherin and beta-catenin was significantly lower in invasive than in noninvasive prolactinomas (P <.002 and P <.005, respectively), and reduced expression of E-cadherin and beta-catenin was more frequent in invasive than in noninvasive prolactinomas (P <.001 and P <.05, respectively); in contrast, gamma-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 beta-catenin predicted high MIB-1 expression (P <.05). Moreover, the expression of E-cadherin and beta-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 alpha-catenin, p120, and clinicopathologic features. In conclusion, the reduction of E-cadherin and beta-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.
authors.affiliation: Department of Pathology, School of Medicine, Tokushima University, Tokushima, Japan.
authors.forename: Zhi Rong
authors.initials: ZR
authors.lastname: Qian
authors.forename: Chiun Chei
authors.initials: CC
authors.lastname: Li
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamasaki
authors.forename: Noriko
authors.initials: N
authors.lastname: Mizusawa
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yoshimoto
authors.forename: Shozo
authors.initials: S
authors.lastname: Yamada
authors.forename: Takashi
authors.initials: T
authors.lastname: Tashiro
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Horiguchi
authors.forename: Shingo
authors.initials: S
authors.lastname: Wakatsuki
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Hirokawa
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sano
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015820:Cadherins / Q000032:analysis; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000032:analysis; D051180:Desmoplakins; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000032:analysis; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000473:pathology*; D015175:Prolactinoma / Q000378:metabolism / Q000473:pathology*; D015534:Trans-Activators / Q000032:analysis; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin; D000095002:Delta Catenin
chemical_list: C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495292:JUP protein, human; D019394:Ki-67 Antigen; D010750:Phosphoproteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin; D000095002:Delta Catenin