Role of E-cadherin, alpha-, beta-, and gamma-catenins, and p120 (cell adhesion molecules) in prolactinoma behavior.
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.
Qian
Zhi Rong
ZR
Department of Pathology, School of Medicine, Tokushima University, Tokushima, Japan.
Li
Chiun Chei
CC
Yamasaki
Hiroyuki
H
Mizusawa
Noriko
N
Yoshimoto
Katsuhiko
K
Yamada
Shozo
S
Tashiro
Takashi
T
Horiguchi
Hidehisa
H
Wakatsuki
Shingo
S
Hirokawa
Mitsuyoshi
M
Sano
Toshiaki
T
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
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