Significance of E-cadherin/beta-catenin complex and cyclin D1 in breast cancer.
E-cadherin and beta-catenin are important epithelial adhesion molecules in normal epithelium. Loss of E-cadherin - beta-catenin adhesion is an important step in the progression of many epithelial malignancies. beta-catenin plays also a role in intracellular signaling and can function as an oncogene when binds to the T-cell factor 4 (Tcf4)-binding site in the promotor region of cyclin D1 and transactivates genes after translocation to the nucleus. We evaluated the immunohistochemical expression pattern of E-cadherin, beta-catenin in relationship with cyclin D1 overexpression, tumor stage, clinicopathologic parameters and patient survival in 128 mammary infiltrating duct carcinomas. The expression of E-cadherin/beta-catenin complex and beta-catenin/cyclin D1 double staining with confocal scanning laser microscope was evaluated. There were aberrant expressions in 78% of E-cadherin, 79% of beta-catenin, and 66% of cyclin D1 in breast cancer. There was correlation of aberrant expression of E-cadherin or beta-catenin with lymph node metastasis, survival rate, and survival length. However, there was no correlation of cyclin D1 overexpression with aberrant expression of E-cadherin or beta-catenin. No death was found in normal expression of beta-catenin, however lowest survival (50%) was found in nuclear beta-catenin expression. There was correlation of overexpression of cyclin D1 with survival rate and survival length. The highest survival rate and survival length were found in membranous normal beta-catenin expression group, however significant decrement of survival length was found in the groups of aberrant expression one or both of E-cadherin or/and beta-catenin. These results suggest that aberrant expression of E-cadherin, beta-catenin, and cyclin D1 may be involved in tumor metastasis, and analysis of the degree or the pattern of E-cadherin, beta-catenin, cyclin D1, and E-cadherin/beta-catenin complex may be good prognostic markers of mammary infiltrating duct carcinoma.
Lim
Sung-Chul
SC
Department of Pathology, College of Medicine, Chosun University Hospital, Dong-ku, Kwangju, Korea. sclim@mail.chosun.ac.kr
Lee
Mi-Sook
MS
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D015820:Cadherins / Q000096:biosynthesis*; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000378:metabolism*; D019938:Cyclin D1 / Q000096:biosynthesis*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D011379:Prognosis; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis*; D016896:Treatment Outcome; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1