Ki67 Proliferation Index in Germinal and Non-Germinal Subtypes of Diffuse Large B-Cell Lymphoma

Abstract

Introduction Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma. The 2016 World Health Organization (WHO) update on hematopoietic tumors suggested that all DLBCL cases should be subtyped into germinal and non-germinal center phenotypes. Ki67 immunohistochemistry is a maker of cell proliferation and thus is used as a prognostic and predictive marker in various tumors of human body. Only a few studies evaluated the proliferative index of DLBCL subtypes in our population. Therefore, in this study, we evaluated the frequency of subtypes of DLBCL in our population and K67 index in each subtype. Methods A retrospective observational study was conducted in the Department of Histopathology, Liaquat National Hospital and Medical College, from January 2018 till December 2020, over a period of three years. A total of 101 cases with a histopathological diagnosis consistent DLBCL were included in the study. Immunohistochemical (IHC) stains CD10, B-cell lymphoma 6 (Bcl-6), and multiple myeloma oncogene 1 (MUM1) were applied for the further sub-categorization of DLBCL into germinal center B-cell-like (GCB) and non-GCB subtypes according to the Hans algorithm. The Ki67 index was interpreted in hot spots of the tumor and reported as an average percentage. Results Out of 101 DLBCL cases, 47.5% of DLBCL were GCB, while 52.5% were non-GCB subtypes. Bcl-2, Bcl-6, MUM1, c-Myc, CD10, and CD30 expression were noted in 62.4%, 45.5%, 42.6%, 44.6%, 39.6%, and 7.9% cases, respectively. The mean Ki67 index was 72.94±16.69%. The mean Ki67 index in non-GCB-type DLBCL was 77.67±14.80%, which was significantly higher than the mean Ki67 index in GCB-type DLBCL (67.70±17.22%) with a significant p-value (p=0.002). Cervical lymph node was the most common site of DLBCL, while the stomach was the most common extra-nodal site. A significant association of Ki67 index was noted with subtypes of DLBCL. A higher proportion of non-GCB-type DLBCL exhibited greater than 80% Ki67 index than GCB subtype DLBCL. Moreover, a significant association Ki67 index was noted with c-Myc positivity. A higher proportion of c-Myc-positive DLBCL had greater than 80% Ki67 index. Conclusion We found that non-GCB-type DLBCL had a higher Ki67 index than GCB subtype DLBCL, portending a poor prognostic significance of non-GCB subtype of DLBCL. Moreover, c-Myc expression was associated with a higher Ki67 index.

Expression of PD-L1 and YWHAZ in Patients with Diffuse Large B Cell Lymphoma: A Possible Association with the Prognosis of Lymphoma

“…A daily examination of bone marrow involvement should be performed to adjust the treatment scheme. The Ki67 index of the non-GCB subtype is higher than that of the GCB subtype, which contradicted the results of this study [ 27 ]. Some studies showed a reverse relationship between the Ki67 index and clinical prognosis, while others did not [ 28 ].…”

Evaluation of Ki-67 as a Prognostic Marker in Diffuse Large B-Cell Lymphoma—A Single-Center Retrospective Cohort Study

“…Moreover, it was claimed that the prognostic value of Ki-67 expression is limited and rather dependent on other patient features, such as bulk and IPI [ 14 ] or age [ 15 ]. It was also found that high Ki-67 expression is more common in non-germinal-center B-cell (non-GCB)-like DLBCL and is associated with c-MYC expression, which might partly explain the poorer outcome in those patients [ 16 ]. However, studies addressing Ki-67, IPI and treatment responses are not well established, as described in a systematic meta-analysis [ 4 ] which found that there is no clear relationship with IPI and that there are too few studies concerning treatment outcomes.…”

Multivariate indicators of disease severity in COVID-19

“…Having the highest standardized canonical discriminant function coefficient value (1.024), MAIT population was the most impactful on the single discriminant function in Model 2 and, thus, on group separation. Group means did not significantly differ for the remaining four variables [CD38 + NK cells (NK cells with enhanced cytotoxicity and cytokine secretion 30 ) (en38NK), CD21 + CD27 − Ki67 + B cells (proliferating/activated naïve B cells 31 , 32 ) (actNB), CD27 + NK cells (NK cells with enhanced function 33 , 34 ) (en27NK), and CD27 − CD45RA + effector memory CD8 + T cells (terminally differentiated effector T cells 35 ) (Temra)]; these variables had relatively high Wilks’ λs (0.960, 0.852, 0.993, and 0.908, respectively), indicating that only small portions of their respective variances were related to group membership (Table 2 ). However, these variables were not useless to the model since incorporating each of them resulted in a highly significant boost to the discriminatory ability of the model—as indicated by the p -values associated with each step (see above and Table 1 )—and a decrease in the model’s Wilks’ λ (Table 1 ).…”