Expression of Cyclin D1 Is Associated with β-Catenin Expression and Correlates with Good Prognosis in Colorectal Adenocarcinoma

Abstract

Background: The aim of this study is to investigate the prevalence and prognostic impact of β-catenin and cyclin D1 expression in colorectal carcinoma (CRC) patients.

Method: We evaluated immunohistochemial expression of β-catenin and cyclin D1 using 2-mm cores from 220 CRC patients for tissue microarray, and its significance was statistically evaluated.

Result: Positive expression of β-catenin and cyclin D1 was found in 72.5% (158 of 218 cases) and 59.4% (129 of 217 cases) of CRC patients, respectively. Expression of β-catenin was significantly correlated with tumor location (P = .017), differentiation (P = .010), lymph node metastasis (P = .032), preoperative carcinoembryonic antigen level (P = .032), and cyclin D1 expression (P = .005). Expression of cyclin D1 was significantly correlated with recurrence and/or metastasis (P = .004). In univariate analysis, β-catenin expression predicted more favorable overall survival (P = .022) and cyclin D1 expression predicted both more favorable overall survival and relapse-free survival (P = .004 and P = .006, respectively). Multivariate analysis showed that tumor stage and expression of cyclin D1 were independent prognostic factors significantly associated with overall survival and relapse-free survival.

Conclusion: This study shows that expression of β-catenin and cyclin D1 is associated with favorable clinicopathologic variables and it is a clinically significant prognostic indicator for CRC patients.

Figure 1

Immunohistochemical staining for β-catenin (A–C) and cyclin D1 (D–F) in normal colorectal mucosa and colorectal adenocarcinoma. Normal mucosa is negative for β-catenin (A) and cyclin D1 (D). In colorectal adenocarcinoma specimens, β-catenin is positive in the nuclei and cytoplasm (B), whereas cyclin D1 show nuclear positivity (E). Some colorectal adenocarcinomas are negative for β-catenin (C) and cyclin D1 (F). Original magnification, x400.

Figure 2

Survival analysis in colorectal adenocarcinoma. (A) Overall survival and relapse-free survival in well/moderately differentiated and poorly differentiated groups. (B) Overall survival and relapse-free survival in lowclinical stage (I and II) and high clinical stage (III and IV) groups. (C) Relationship of nuclear β-catenin expression to overall survival and relapse-free survival. (D) Relationship of nuclear cyclin D1 expression to overall survival and relapse-free survival. P values were determined by comparing survival distributions using the log-rank test.

Figure 3

Survival analysis in colorectal adenocarcinoma patients who had received adjuvant chemotherapy. (A) Relationship of nuclear β-catenin expression to overall survival and relapse-free survival. (B) Relationship of nuclear cyclin D1 expression to overall survival and relapse-free survival. P values were determined by comparing survival distributions using the log-rank test.