Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas

A prospective Southwest Oncology Group trial

T. P. Miller, T. M. Grogan, S. Dahlberg, C. M. Spier, Rita Braziel, P. M. Banks, K. Foucar, C. R. Kjeldsberg, N. Levy, B. N. Nathwani, B. Schnitzer, R. R. Tubbs, E. R. Gaynor, R. I. Fisher

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Abstract

The growth fraction of tumors from patients with non-Hodgkin's lymphomas (NHL) has been shown to correlate with survival in retrospective studies. The growth fraction can be evaluated using immunohistochemical techniques employing the Ki-67 monoclonal antibody (MoAb) that marks a nuclear protein present in cycling cells. The purpose of this study was to evaluate the clinical utility of the Ki-67 MoAb for predicting survival. Using a prospective trial design in a multi-institutional cooperative trials group, the proliferative index, clinical outcome, and statistical correlations were independently assessed for previously untreated patients with advanced stages of intermediate- and high-grade histologies of NHL treated on Southwest Oncology Group study (SWOG 8516, Intergroup 0067). The proportion of Ki-67- positive cells was determined on snap-frozen thin tissue sections. A proliferative index of 80% or greater, as determined from prior retrospective studies, identified a group of patients (18%) who had a poor outcome. Overall survival was significantly reduced in these patients with a high Ki-67- associated proliferative index compared with those with a low proliferative index (P = .001). One-year survival estimates were 82% (low proliferative index) versus 18% (high proliferative index). A multivariate regression analysis incorporating commonly used clinical prognostic features confirmed the independent effect of proliferation on survival (relative risk estimate 5.9; 95% confidence interval, 2.2, 16.1). The Ki-67 MoAb identifies a group of patients with rapidly fatal NHL for whom currently available chemotherapy is inadequate.

Original languageEnglish (US)
Pages (from-to)1460-1466
Number of pages7
JournalBlood
Volume83
Issue number6
StatePublished - Mar 15 1994
Externally publishedYes

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Oncology
Non-Hodgkin's Lymphoma
Monoclonal Antibodies
Antigens
Survival
Histology
Chemotherapy
Nuclear Proteins
Regression analysis
Retrospective Studies
Tumors
Cells
Tissue
Growth
Multivariate Analysis
Regression Analysis
Confidence Intervals
Drug Therapy
Neoplasms

ASJC Scopus subject areas

  • Hematology

Cite this

Miller, T. P., Grogan, T. M., Dahlberg, S., Spier, C. M., Braziel, R., Banks, P. M., ... Fisher, R. I. (1994). Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas: A prospective Southwest Oncology Group trial. Blood, 83(6), 1460-1466.

Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas : A prospective Southwest Oncology Group trial. / Miller, T. P.; Grogan, T. M.; Dahlberg, S.; Spier, C. M.; Braziel, Rita; Banks, P. M.; Foucar, K.; Kjeldsberg, C. R.; Levy, N.; Nathwani, B. N.; Schnitzer, B.; Tubbs, R. R.; Gaynor, E. R.; Fisher, R. I.

In: Blood, Vol. 83, No. 6, 15.03.1994, p. 1460-1466.

Research output: Contribution to journalArticle

Miller, TP, Grogan, TM, Dahlberg, S, Spier, CM, Braziel, R, Banks, PM, Foucar, K, Kjeldsberg, CR, Levy, N, Nathwani, BN, Schnitzer, B, Tubbs, RR, Gaynor, ER & Fisher, RI 1994, 'Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas: A prospective Southwest Oncology Group trial', Blood, vol. 83, no. 6, pp. 1460-1466.
Miller, T. P. ; Grogan, T. M. ; Dahlberg, S. ; Spier, C. M. ; Braziel, Rita ; Banks, P. M. ; Foucar, K. ; Kjeldsberg, C. R. ; Levy, N. ; Nathwani, B. N. ; Schnitzer, B. ; Tubbs, R. R. ; Gaynor, E. R. ; Fisher, R. I. / Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas : A prospective Southwest Oncology Group trial. In: Blood. 1994 ; Vol. 83, No. 6. pp. 1460-1466.
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abstract = "The growth fraction of tumors from patients with non-Hodgkin's lymphomas (NHL) has been shown to correlate with survival in retrospective studies. The growth fraction can be evaluated using immunohistochemical techniques employing the Ki-67 monoclonal antibody (MoAb) that marks a nuclear protein present in cycling cells. The purpose of this study was to evaluate the clinical utility of the Ki-67 MoAb for predicting survival. Using a prospective trial design in a multi-institutional cooperative trials group, the proliferative index, clinical outcome, and statistical correlations were independently assessed for previously untreated patients with advanced stages of intermediate- and high-grade histologies of NHL treated on Southwest Oncology Group study (SWOG 8516, Intergroup 0067). The proportion of Ki-67- positive cells was determined on snap-frozen thin tissue sections. A proliferative index of 80{\%} or greater, as determined from prior retrospective studies, identified a group of patients (18{\%}) who had a poor outcome. Overall survival was significantly reduced in these patients with a high Ki-67- associated proliferative index compared with those with a low proliferative index (P = .001). One-year survival estimates were 82{\%} (low proliferative index) versus 18{\%} (high proliferative index). A multivariate regression analysis incorporating commonly used clinical prognostic features confirmed the independent effect of proliferation on survival (relative risk estimate 5.9; 95{\%} confidence interval, 2.2, 16.1). The Ki-67 MoAb identifies a group of patients with rapidly fatal NHL for whom currently available chemotherapy is inadequate.",
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AU - Nathwani, B. N.

AU - Schnitzer, B.

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