p21^<WAF1/CIP1> and Ki-67 Expression of Serrated Adenoma of the Colorectum : An Investigation of Cell Differentiation/Maturation and its Relationship with Cell Proliferation

The immunohistochemical expression of p21^<WAF1/CIP1> and Ki-67 of serrated adenoma (SA) (n=19) of the colorectum was evaluated in order to elucidate its cell differentiation/maturation status and its relationship with cell proliferation. This was then compared with those of a hyperplastic polyp (HP) (n=18), traditional tubular adenoma (TA) (n=21), and normal colonic mucosa (n=11). Longitudinally sectioned hemicrypts were selected from each sample, and the percentage of the p21^<WAF1/CIP1> (+) portion and the proliferative zone (PZ) per entire hemicrypt length were determined. In SA, although the topographic regulation of cell differentiation/maturation and proliferation was maintained, the percentage of PZ (26.5±1.8%) decreased and that of the p21^<WAF1/CIP1> (+) portion (61.4±2.1%) increased compared with those of normal colonic mucosa (31.8±1.3% and 30.6±1.4%) (p<0.05, respectively), indicating that the cell kinetic balance of SA was inclined toward cell differentiation/maturation. A similar cell kinetic imbalance was seen in HP, whereas the cell kinetic balance was inclined toward cell proliferation in TA. These findings suggest that, unlike TA, SA is a disorder of cell differentiation/maturation rather than cell proliferation, and the elongation of the cell life span and the subsequent reduction of exfoliation, which are the known fundamental cell kinetics of HP, may contribute to its neoplastic growth.