Downregulation of E-cadherin and its undercoat proteins in pituitary growth hormone cell adenomas with prominent fibrous bodies.
The cadherin-catenin complex regulates cellular adhesion and motility, and genetic alterations in these molecules play a critical role in multistage tumorigenesis. In this study, the expression of three major type I classic cadherins E-, N-, and P-cadherin and their undercoat proteins alpha-, beta-, and gamma-catenin, and pp120 was investigated in 127 pituitary adenomas and 10 normal adenohypophyseal glands using an immunohistochemical technique with highly specific monoclonal antibodies. In normal pituitary glands, E-cadherin, catenins, and pp120 were strongly expressed on almost all hormone-producing cell-cell boundaries, N-cadherin was weakly immunoreactive on a few cell-cell boundaries, and P-cadherin was negative. In pituitary adenomas, a correlation was not identified among expression of E-cadherin, catenins, or pp120 with patient age, sex, hormone level, tumor size, and/or invasiveness, respectively. Expression of E-cadherin, catenins, and pp120 was significantly reduced in 24 growth hormone (GH) cell adenomas with prominent fibrous bodies compared with the other subtypes of pituitary adenomas and normal pituitary glands (p < 0.0001, respectively). Methylation-specific polymerase chain reaction analysis revealed that the E-cadherin gene promoter region was methylated in 6 of 16 (37.5%) GH cell adenomas with prominent fibrous bodies examined, 2 of which displayed total methylation, but not in 10 GH cell adenomas without fibrous bodies. No mutation of exon 3 of the beta-catenin gene was found in 16 GH cell adenomas with prominent fibrous bodies or in 10 other subtypes of pituitary adenomas that showed unremarkable intracellular presence of beta-catenin protein. In conclusion, the decreased expression of the E-cadherin catenin complex and methylation of the E-cadherin gene promoter region only in GH cell adenomas with prominent fibrous bodies may be an event associated with the formation of fibrous bodies.
Xu
Bing
B
Department of Pathology, University of Tokushima School of Medicine, Tokyo, Japan.
Sano
Toshiaki
T
Yoshimoto
Katsuhiko
K
Yamada
Shozo
S
D000236:Adenoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D015820:Cadherins / Q000032:analysis* / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics; D019175:DNA Methylation; D051180:Desmoplakins; D015536:Down-Regulation; D005091:Exons; D019382:Human Growth Hormone / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D010911:Pituitary Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495292:JUP protein, human; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin; D019382:Human Growth Hormone