Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas: a prospective Southwest Oncology Group trial

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.

Bcl‐2, Bcl‐6, and the International Prognostic Index are prognostic indicators in patients with diffuse large B‐cell lymphoma treated with rituximab‐containing chemotherapy

“…Ki‐67 index, cMyc index, starry sky pattern, and necrosis are considered to be correlated immunohistochemical and histopathological findings, and all of them are associated with proliferation activity of tumors. High Ki‐67 index and high cMyc index reflecting cMYC rearrangement were reported to be poor prognostic parameters . The predictive value of Ki‐67 index was reported in the pre‐rituximab era .…”

“…Immunohistochemical expression of Bcl‐2 and CD5 has been reported to be associated with an unfavorable prognosis; expression of Bcl‐6 and CD10 are associated with a favorable prognosis. High Ki‐67 index has also been reported to be a poor prognostic parameter. However, these results were obtained mainly in the pre‐rituximab era.…”

MIB‐1 labeling index as a prognostic factor for patients with follicular lymphoma treated with rituximab plus CHOP therapy

“…Furthermore, similar to our findings, they reported that the histological grade did not predict the outcome. (5) Miller et al (6) and Martin et al (7) found that the MIB-1 labeling index correlated with OS but not with PFS. However, in the study of Martin et al, (7) significance was not detected by the multivariate analysis.…”

“…(5) Miller et al (6) and Martin et al (7) found that the MIB-1 labeling index correlated with OS but not with PFS. However, in the study of Martin et al, (7) significance was not detected by the multivariate analysis. Wang et al (8) reported that patients with low-grade FL and a high proliferation index determined by MIB-1 labeling index tended to have a shorter OS (P = 0.087) than those with a low proliferation index.…”

Association of quantitative assessment of the intrafollicular proliferation index with outcome in follicular lymphoma

“…The PI is known to be an important predictor of outcome in diffuse large B cell lymphoma and MCL (Miller et al, 1994;Schaffel et al, 2010) as well as solid tumours, such as breast and prostate cancer (Scholzen & Gerdes, 2000), but its role in FL is not well established. A few previous studies have addressed this question in somewhat different ways (Wang et al, 2005;Klapper et al, 2007;Koster et al, 2007).…”