Frequent microsatellite alterations at chromosomes 9p21 and 3p14 in oral premalignant lesions and their value in cancer risk assessment.

To better understand genetic alterations in oral premalignant lesions, we examined 84 oral leukoplakia samples from 37 patients who had been enrolled in a chemoprevention trial. The samples were analyzed for two microsatellite markers located at chromosomes 9p21 and 3p14. Loss of heterozygosity (LOH) at either or both loci was identified in 19 of the 37 (51%) patients. Of these 19 patients, seven (37%) have developed head and neck squamous cell carcinoma (HNSCC) while only one of 18 (6%) of patients without LOH developed HNSCC. Our data suggest that clonal genetic alterations are common in oral premalignant lesions; that multiple genetic alterations have already occurred in oral premalignant lesions, allowing at least a focal clonal expansion; and that losses of the 9p21 and 3p14 regions may be related to early processes of tumorigenesis in HNSCC. These genetic alterations in premalignant tissues may serve as markers for cancer risk assessment.

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.