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

Vincent S. Khoo, Alan Pollack, Didier Cowen, Daryl Lim Joon, Nalini Patel, Nicholas H A Terry, Gunar K. Zagars, Andrew C. Von Eschenbach, Marvin L. Meistrich, Patricia Troncoso

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)166-172
Number of pages7
JournalProstate
Volume41
Issue number3
DOIs
StatePublished - Nov 10 1999
Externally publishedYes

Fingerprint

Ploidies
S Phase
Prostatic Neoplasms
Radiotherapy
Prostate-Specific Antigen
Neoplasm Grading
DNA
Diploidy
Treatment Failure
Actuarial Analysis
Neoplasms
Transurethral Resection of Prostate
Tetraploidy
Aneuploidy
Staining and Labeling
Recurrence
Serum

Keywords

  • DNA-ploidy
  • Ki-67
  • MIB-1
  • Prostate cancer
  • Prostate-specific antigen
  • Radiotherapy

ASJC Scopus subject areas

  • Urology

Cite this

Relationship of Ki-67 labeling index to DNA-ploidy, S-phase fraction, and outcome in prostate cancer treated with radiotherapy. / Khoo, Vincent S.; Pollack, Alan; Cowen, Didier; Joon, Daryl Lim; Patel, Nalini; Terry, Nicholas H A; Zagars, Gunar K.; Von Eschenbach, Andrew C.; Meistrich, Marvin L.; Troncoso, Patricia.

In: Prostate, Vol. 41, No. 3, 10.11.1999, p. 166-172.

Research output: Contribution to journalArticle

Khoo, VS, Pollack, A, Cowen, D, Joon, DL, Patel, N, Terry, NHA, Zagars, GK, Von Eschenbach, AC, Meistrich, ML & Troncoso, P 1999, 'Relationship of Ki-67 labeling index to DNA-ploidy, S-phase fraction, and outcome in prostate cancer treated with radiotherapy', Prostate, vol. 41, no. 3, pp. 166-172. https://doi.org/10.1002/(SICI)1097-0045(19991101)41:3<166::AID-PROS3>3.0.CO;2-E
Khoo, Vincent S. ; Pollack, Alan ; Cowen, Didier ; Joon, Daryl Lim ; Patel, Nalini ; Terry, Nicholas H A ; Zagars, Gunar K. ; Von Eschenbach, Andrew C. ; Meistrich, Marvin L. ; Troncoso, Patricia. / Relationship of Ki-67 labeling index to DNA-ploidy, S-phase fraction, and outcome in prostate cancer treated with radiotherapy. In: Prostate. 1999 ; Vol. 41, No. 3. pp. 166-172.
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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.",
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T1 - Relationship of Ki-67 labeling index to DNA-ploidy, S-phase fraction, and outcome in prostate cancer treated with radiotherapy

AU - Khoo, Vincent S.

AU - Pollack, Alan

AU - Cowen, Didier

AU - Joon, Daryl Lim

AU - Patel, Nalini

AU - Terry, Nicholas H A

AU - Zagars, Gunar K.

AU - Von Eschenbach, Andrew C.

AU - Meistrich, Marvin L.

AU - Troncoso, Patricia

PY - 1999/11/10

Y1 - 1999/11/10

N2 - 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.

AB - 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.

KW - DNA-ploidy

KW - Ki-67

KW - MIB-1

KW - Prostate cancer

KW - Prostate-specific antigen

KW - Radiotherapy

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