Correlation between c-myc protein expression and phases of the cell cycle in human colorectal carcinomas

There is a direct correlation between the overexpression of the c-myc product and the clinicopathological state of patients with colorectal carcinomas. This study was carried out to understand the reasons for this. In vitro, S-phase synchronous culture was performed using the human colon carcinoma cell lines, COLO201 and SW480; and thymidine-hydroxyurea blockage was carried out. The proportion of c-myc protein-positive cells decreased gradually with progressive stage of the cell cycle, as determined by flow cytometry (FCM) and Western blot analysis. A rapid decrease in the number of c-myc protein-positive cells in the GO G1-phase was the main reason for the complete loss of c-myc protein expression in the S-phase of synchronous culture, although the percentage of these cells was higher in the S and G2M-phases than in the GOG1-phase after each initiation of synchronous culture. These findings suggest that the c-myc protein-positive cells which were arrested in the G1-phase could play an important role in cell proliferation. In another study, 46 paraffin-embedded specimens of human colorectal carcinomas were examined for c-myc protein expression by flow cytometry (FCM). Patients with higher expression in the GOG1-phase (% positive cells > or = mean) showed significantly lower rates of survival (p = 0.004), as determined using the generalized Wilcoxon's method, and this higher expression correlated with aneuploid carcinoma (p = 0.005), with metastasis to the lymph nodes (p = 0.003), with the degree of regional lymph node metastasis (p = 0.02), and with the depth of wall-infiltration by the carcinoma (p = 0.006), as determined using the chi square test. Liver metastases and peritoneal dissemination did not correlate with c-myc protein expression. Analyses of all phases were carried out, however, similar results were obtained by analyzing only the GOG1-phase of the cell cycle. Therefore, it would seem that determination of c-myc protein expression in a carcinoma, especially in the G1-phase of the cell cycle, would be useful as a marker of tumor progression and for evaluation of the clinical prognosis of patients with colorectal carcinomas.