Expression of beta-Catenin, c-Myc, and Cyclin D1 in Pulmonary Adenocarcinomas

ABSTRACT

BACKGROUND: beta-Catenin has dual functions adhesive molucule and transcriptional activator. Subcellular accumulation of beta-catenin and subsequent formation of beta-catenin- Tcf/Lef-1 complexes, as well as c-myc and cyclin D1 genes which were recently defined as target genes of beta-catenin- Tcf/Lef-1, has been shown to be important in the development of colorectal and breast carcinomas. The author investigated the rate of subcellular accumulation of beta-catenin and overexpression of c-myc and cyclin D1, and also investigated the association between them in the pulmonary adenocarcinomas. METHODS: Fifty-one surgically resected primary adenocarcinomas of the lung, including 11 bronchioloalveolar carcinomas, were investigated by immunohistochemical analysis with monoclonal antibodies specific for beta-catenin, c-myc and cyclin D1. Clinico-pathological information were collected from the patient charts and surgical pathology reports. RESULTS: Accumulation of beta-catenin in the nucleus and/or cytoplasm and overexpression of c-myc and cyclin D1 were observed to be 20%, 37%, 16%, respectively. Ten cases showing accumulated patterns of beta-catenin revealed alternative overexpressions of c-myc (7 cases) and cyclin D1 (3 cases). In nonmucinous tumors, 9 cases showing overexpression of c-myc or cyclin D1 revealed accumulations of beta-catenin. The accumulation of beta-catenin was not statistically related to clinico-pathological parameters. The association between c-myc overexpression and histological subtype of tumors was observed. CONCLUSIONS:It is suggested that the accumulation of beta-catenin is closely associated with tumorigenesis in a minor subset (20%) of peripheral adenocarcinomas of the lung. It is also suggested that transactivation of beta-catenin may closely be associated with the overexpression of c-myc or cyclin D1 in the nonmucinous adenocarcinoma.