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

Abstract

BACKGROUND Our purpose was to evaluate the relationship of Ki‐67 labeling index (Ki67‐LI) to deoxyribonucleic acid (DNA) ploidy, S phase fraction (SPF), other clinical prognostic factors, and clinical outcome for patients with 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 (diploid + near‐diploid) and nondiploid (tetraploid + aneuploid). Immunohistochemical staining of Ki‐67 by the MIB‐1 monoclonal antibody was used to calculate Ki67‐LI. Median patient follow‐up was 62 months. Treatment failure was defined 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 stage, Gleason score, and pretreatment PSA. Nondiploid tumors had significantly higher Ki67‐LIs, as did patients who failed radiotherapy over the follow‐up period. SPF was not significantly correlated with Ki67‐LI. As a categorical variable, the most significant relationships were seen when Ki67‐LI was subdivided into thirds around the median (Ki67‐LI ≤1.5%, Ki67‐LI >1.5–3.5%, and Ki67‐LI >3.5%). This trichotomous variable correlated significantly with pretreatment PSA (P = 0.0008), tumor stage (P = 0.016), Gleason score (P = 0.024), and treatment failure (P = 0.0015), but not with DNA‐ploidy (P = 0.15). In actuarial univariate analyses, Ki67‐LI appeared to be a more significant predictor of patient outcome (P = 0.003) than DNA‐ploidy (P = 0.035). CONCLUSIONS The Ki67‐LI correlated with known prognostic factors such as pretreatment PSA, tumor stage, and Gleason score, and was also weakly related to DNA‐ploidy. In comparison to DNA‐ploidy, Ki67 LI seems to be a better correlate of treatment outcome. Prostate 41:166–172, 1999. © 1999 Wiley‐Liss, Inc.

Diagnostic and prognostic molecular biomarkers for prostate cancer

“…Ki-67 is prognostic for death in patients of watchful waiting cohorts, [198][199][200] prognostic for biochemical relapse in cohorts of patients treated by radical prostatectomy, [201][202][203][204][205][206][207] and is prognostic for disease progression in patients undergoing radiation. [208][209][210][211][212] In most of these studies, Ki-67 has an independent prognostic value, which implies that it does add prognostic information upon Gleason score and serum PSA levels. In spite of this apparently overwhelming evidence from multiple independent studies, which probably make it the most oftenconfirmed prognostic biomarker, Ki-67 has still not entered clinical practice.…”

Tissue Biomarkers for Prostate Cancer Radiation Therapy

“…An even more limited number of studies have produced mixed results after examining DNA ploidy as a biomarker for prostate cancer patients treated with radiation therapy [80-85]. …”

“…The Ki-67 antigen is a biomarker used to determine proliferative rate for many other types of tumors [120], as well as been shown to correlate with clinical outcomes of prostate cancer patients treated with surgery or radiation therapy [80, 108, 109, 121-128]. One previous study had suggested a Ki-67 index of ≥3.5% was prognostic for PSA failure following radiation therapy [126].…”

Utilidad de la expresión de Ki67 en las biopsias preoperatorias para predecir la recidiva bioquímica del cáncer de próstata después de la prostatectomía radical

“…La expresión media de células con Ki67 era de 7,5% y tenía un alto poder predictivo para la supervivencia. Khoo VS et al en 1999 46 contrastaron la relación entre Ki67 y ploidía con la evolución del cáncer de próstata después de tratamiento con radioterapia externa. En los resultados distinguieron 3 categorías de tumores: Tumores con positividad de Ki67 ≤al 1,5%; tumores con positividad de Ki67 entre 1,5 y 3,5%; tumores con positividad de Ki67 en un porcentaje mayor del 3,5%.…”