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.

Ki‐67 expression as a prognostic factor in diffuse large B‐cell lymphoma patients treated with rituximab plus CHOP

“…To the best of our knowledge, the present study is the first to assess the significance of Ki-67 expression in a sizable DLBCL patient cohort receiving a rituximab-containing regimen. High Ki-67 expression was associated with shorter OS and EFS, and higher relapse rates, consistent with previous data from the non-rituximab era on a prospective analysis of DLBCL (11), and mantle cell lymphoma treated with a rituximab-containing regimen (20). Our results indicated that the replication index was not related to the response of tumors to rituximab plus chemotherapy, in agreement with a previous report (21).…”

“…However, strong p53 protein expression was correlated with p53 mutations, and prognostic significance for DLBCL patients treated with R-CHOP was maintained (29). The prognostic value of Ki-67 expression in DLBCL is still a controversial issue, although the prevailing concept is that high Ki-67 expression is associated with poor survival (9)(10)(11)(12)(14)(15)(16)(17)(18)(19). Variable results among study groups may result from diverse study populations, sample sizes, method of Ki-67 staining ⁄ assessment, chosen Ki-67 threshold, and heterogeneous therapeutic regimens.…”

Posttransplantation lymphoproliferative disorder in liver recipients: Characteristics, management, and outcome

“…We did not find a correlation between the proliferative index (the proportion of Ki67-positive cells to tumor cells) and survival, as previously reported. 17 Four patients died; however, their proliferative index was less than 80%. A larger sample is needed to clarify this issue.…”

Prognostic clinicopathologic factors, including immunologic expression in diffuse large B‐cell lymphomas

“…However, other studies have shown that a high Ki-67 proliferation index is also a poor prognostic marker for DLBCL. 5,11 Overexpression of the P-glycoprotein product of mdr-1 gene is a well-characterized mechanism of drug resistance. Lee et al reported that strong MDR-1 immunoreactivity (Ͼ 50%) was an independent negative predictor of overall survival in canine lymphomas.…”