Background. With the recent development of molecular markers, it has become possible to characterize colorectal carcinomas beyond clinical and histologic aspects. When considered together with tumor stage, molecular markers will allow us further insight into individual tumor biologies and prognoses. Purpose. To investigate the expression and prognostic implications of the molecular markers, p53, bcl-2, Rb, hMLH1, hMSH2, β-catenin, E-cadherin, and MUC-2. Methods. We analyzed the clinical, histologic, and molecular factors for 229 patients with colorectal carcinoma of stage II and III and compared their prognoses.Weused tissue microarrays to analyze the expressions of molecular markers and to assess their correlations with prognosis. Semiquantitative expressions of molecular markers and clinicopathologic parameters were analyzed with respect to prognosis. Results. Among the clinicopathologic parameters, leftsided location, age older than 70 years, higher preoperative serum carcinoembryonic antigen (CEA) level (≤ 5 ng/mL), irregular growth pattern, and perineural invasion were significantly related to poor prognosis in stage II and III patients. For molecular factors, loss of expression of E-cadherin and MUC-2 showed significant correlation with poor overall survival in both cancer stages. Multivariate analysis showed that higher TNM stage, higher preoperative serum CEA level (≤ 5 ng/mL), perineural tumor cell invasion, and loss of E-cadherin and MUC-2 expressions were independently correlated with poor overall survival. Conclusions. Our results indicated that of the analyzed molecular markers, MUC-2 and E-cadherin might be useful in predicting prognosis and planning for adjuvant therapy in patients with stage II and III colorectal carcinomas.
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Patients who had received curative resection (R0) for the treatment of colorectal carcinoma between 1996 and 1999 were enrolled in this study. Patients with multiple primary malignant tumors in other organs, hereditary cancer syndromes, or a history of treatment for previous malignancy were excluded. Patients with double primary malignancy in other organs were excluded. One of the important purposes of this study was to search for surrogate markers that will help to identify the patients for whom the postoperative adjuvant chemotherapy will confer a benefit. We therefore excluded patients who received preoperative chemo-or chemoradia-tion therapy, palliative resectioning (R1 or R2), those whose surgeries were performed in emergency settings, or whose tumor tissues were not available. Specimens were obtained from the archive of the Department of Pathology, Yonsei University, Seoul, Korea. Some of the specimens were obtained from the Liver Cancer Specimen Bank of the National Research Resource Bank Program of the Korea Science and Engineering Foundation of the Ministry of Science and Technology. Fresh, snap-frozen samples obtained during surgery by cryofractionation were used for analysis of microsatellite instability (MSI), and formalin-fixed, paraffin-embedded samples were used for tissue microarray and histologic evaluations. Patient data were registered in the colorectal cancer database of the Department of Surgery and were followed up prospectively. The median follow-up after surgery in December 2007 was 108 months.
ACKNOWLEDGMENT This work was supported by a grant of the Korea Healthcare technology R&D project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A084877).
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