Ki-67 and subtype as prognostic and predictive markers of diffuse large B-Cell lymphoma

Introduction: Since patients with similar International Prognostic Index (IPI) scores have varied outcomes, molecular signatures including Ki-67 overexpression have been studied to prognosticate diffuse large B-cell lymphoma (DLBCL), which have shown varied outcomes. Objective: To correlate Ki-67 expression with survival in two biologic subgroups of DLBCL. Materials and Methods: One hundred and twelve adults with DLBCL between 2008 and 2012 were identified. Ki-67 overexpression was determined using immunohistochemistry. Results: A total of 112 patients of DLBCL were identified and included in the study. The median age was 54 years (18–78 years), with a male/female ratio of 1.8:1. Median survival was greater in patients with low Ki-67 (n = 32) as compared to high Ki-67 (n = 44) (32 m vs. 21.5 m, P = 0.033). In the germinal center B-cell (GCB) subtype, low Ki-67 had a better survival as compared to high Ki-67 (35 m vs. 28 m, P = 0.044), whereas in the non-GCB (NGCB) subtype, the results were same but statistically insignificant (26.5 m vs. 18 m, P = 0.7). In the high IPI arm, low Ki-67 had a better survival (26.5 m vs. 17 m, P = 0.02), whereas in low IPI arm, the results were similar but statistically insignificant (39 m vs. 38 m, P = 0.837). Survival analysis was done in each treatment arm (CHOP and R-CHOP) based on Ki-67 expression (high or low) in GCB and NGCB arms. No statistically significant difference was noted in any of the four arms; 27.5 m versus 34 m (P = 0.738) in high versus low Ki-67 in CHOP-GCB arm, 15 m versus 22 m (P = 0.443) in high versus low Ki-67 in CHOP-NGCB arm, 27 m versus 44 m (P = 0.104) in high versus low Ki-67 in R-CHOP-GCB arm, and 31 m versus 35 m (P = 0.861) in high versus low Ki-67 in R-CHOP-NGCB arm. Conclusions: Ki-67 although an indicator of poor outcome, its use to predict outcomes alone in the absence of study of expression of concomitant markers such as myc/BCL6 would cause a bias in results. Furthermore, its relevance in the rituximab era needs further validation.