Relationship of Ki-67 labeling index to DNA-ploidy, S-phase fraction, and outcome in prostate cancer treated with radiotherapy

BACKGROUND. Our purpose was to evaluate the relationship of Ki-67 labeling index (Ki67-LI) to deoxyribonucleic acid (DNA) ploidy, S phase fraction (SP F), other clinical prognostic factors, and clinical outcome for patients wi th prostate cancer treated by external beam radiotherapy. METHODS. Tissue was retrieved from 42 patients who underwent transurethral resection of the prostate before treatment with external beam radiotherapy between 1987-1993. DNA histogram profiles were classified as diploid (diplo id + near-diploid) and nondiploid (tetraploid + aneuploid). Immunohistochem ical staining of Ki-67 by the MIB-1 monoclonal antibody was used to calcula te Ki67-LI. Median patient follow-up was 62 months. Treatment failure was d efined as two consecutive rises in serum prostate-specific antigen (PSA) or clinical evidence of disease recurrence. RESULTS. The mean and median Ki67-LIs were 3.1 and 2.4, respectively (range , 0-12.4). Mean Ki67-LI values were significantly associated with higher st age, Gleason score, and pretreatment PSA. Nondiploid tumors had significant ly higher Ki67-LIs, as did patients who failed radiotherapy over the follow -up period. SPF was not significantly correlated with Ki67-LI. As a categor ical variable, the most significant relationships were seen when Ki67-LI wa s subdivided into thirds around the median (Ki67-LI less than or equal to 1 .5%, Ki67-LI >1.5-3.5%, and Ki67-LI >3.5%). This trichotomous variable corr elated significantly with pretreatment PSA (P = 0.0008), tumor stage (P = 0 .016), Gleason score (P = 0.024), and treatment failure (P = 0.0015), but n ot with DNA-ploidy (P = 0.15). In actuarial univariate analyses, Ki67-LI ap peared to be a more significant predictor of patient outcome (P = 0.003) th an DNA-ploidy (P = 0.035). CONCLUSIONS. The Ki67-LI correlated with known prognostic factors such as p retreatment PSA, tumor stage, and Gleason score, and was also weakly relate d to DNA-ploidy. In comparison to DNA-ploidy, Ki67 LI seems to be a better correlate of treatment outcome. (C) 1999 Wiley-Liss, Inc.