Objective: Serial colonoscopic observations were prospectively conducted to elucidate the natural history of nonpolypoid tumors. Furthermore, to clarify whether cell kinetic status affects the tumor development, proliferative indices, apoptotic indices, and K-ras codon 12 point mutations on biopsy specimens were investigated.
Methods: Seventy-five colorectal tumors, 13 polypoid and 62 nonpolypoid type (56 flat elevated and six depressed type) were studied. Proliferating and apoptotic cells were detected with anti-Ki-67 antibody and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method, respectively. Point mutations at K-ras codon 12 were examined by enriched polymerase chain reaction-based restriction fragment length polymorphism assay.
Results: The average follow-up period was 22 months (range 1-50). The lesions of subsequent exophytic growth, unchanged shape, depressed growth, and disappearance were observed in 0%, 92%, 0%, and 8% of polypoid type, in 39%, 39%, 13%, and 9% of flat elevated type, and in 33%, 67%, 0%, and 0% of depressed type, respectively. There was no significant difference in tumor size between initial and follow-up colonoscopy. Nonpolypoid tumors apparently changed to the exophytic growth during 2 yr or more. The tumors with exophytic growth had significantly higher proliferative indices/apoptotic indices ratios than those with unchanged morphology and disappearance/depressed growth (p < 0.05, respectively). K-ras codon 12 point mutations did not correlate with tumor development.
Conclusions: Cell kinetic status plays an important role in determining minute colorectal tumor development, but not K-ras codon 12 mutations. Minute nonpolypoid adenomas frequently tend to grow slowly, and nearly 40% of those become the exophytic growth with time. Most of minute nonpolypoid tumors seem to follow the adenoma-carcinoma sequence.