Assessment of Ki-67-derived tumor proliferative activity in colorectal adenocarcinomas

Analysis of tumor growth fraction (TGF) has become essential as cell cycle-directed modalities have been increasingly used for the treatment of solid neoplasms. We studied TGF in fresh tissue samples from 74 surgically resected colorectal carcinomas (50 colon and 24 rectum; 44 men and 30 women) by flow cytometry (FCM) and by immunostaining using Ki-67 monoclonal antibody. In 12 cases, samples of uninvolved colonic mucosa adjacent to tumor (transitional mucosa) and samples of normal mucosa (at least 5 cm away from tumor) were available for growth fraction analysis. The mean Ki-67 and S-phase values were 17.1% (range, 0-60%) and 17.5% (range, 3-39%), respectively. The mean percentage of Ki-67 positivity in tumor samples from women was significantly lower than that in samples from men (P = 0.001). Ki-67-derived TGF values, however, did not correlate with patient age, lymph node status, or tumor size, site, stage, degree of differentiation, or DNA ploidy. The correlation between Ki-67-derived and FCM-derived TGF values was statistically significant (P = 0.001) but marginal (R = 0.35). In both transitional and normal colonic mucosa samples, Ki-67 positivity was mainly confined to the lower half of the crypts, and their growth fraction values were significantly lower than those of tumor tissue; however, there was no difference in values between transitional and normal mucosae. Our results indicate that Ki-67-derived TGF does not correlate with known prognostic factors for colorectal carcinoma; however, long-term follow-up information will be necessary to define the clinical value of Ki-67 staining.