Assessment of Cell Proliferation in Primary and Recurrent Colorectal Cancers -Expression of Transforming Growth Factor-a and Proliferating Cell Nuclear Antigen and Flow Cytometric DNA Analysis

Cell proliferation potential has been found to be a significant biological parameter correlated with the clinical outcome. This study was ta investigate the cell proliferation potential in primary and recurrent colorectal tumor tissues. Using paraffin-embedded tissues from the paired primary and recurrent tumors of l0 patients, a simple hematoxylineosin stain was done and immunohistochemical stains for trans- forming growth factor-a(TGF-a) and proliferating cell nuclear antigen(PCNA) were performed through a labeled streptavidine biotin method. DNA contents and S-phase fraction(SPF) of the cells were assessed by flowcytometric DNA analysis. The degree of differentiation was poorer in the recurrent tumors than in primary tumors. In 4 primary tumors with mixed adenocacinoma and mucinous adenocarcinoma, only the mucinous adenocarcinoma companent was shown in the recurrent tumors. There was no difference in TGF-a expression between the primary and the recurrent tumors however, PCNA was overexpressed in the recurrent tumors comparing to the primary tumors. Flow cytometric DNA analysis was successful in 7 paired cases. There was change of the ploidy from the diploidy to the aneuploidy in 4 cases. SPF showed remarkable increase in the recurrent tumors comparing to the primary tumors. These results show high proliferative potential of the recurrent colorectal tumors, which can be measured using PCNA expression and SPF as biomarkers. Based on the results of this study, an effort to establish more refined method to predict recurrence should be pursued.ope