Prognostic Significance of Ki-67 Nuclear Proliferative Antigen, bcl-2 Protein, and p53 Expression in Follicular and Diffuse Large B-Cell Lymphoma

Abstract

We analyzed 104 patients with non-Hodgkin's lymphoma, follicular or diffuse large-B-cell-type lymphoma, in order to evaluate the correlation between clinical characteristics and immunohistochemical parameters. Immunostaining was performed by means of monoclonal antibodies against Ki-67, bcl-2, and p53 expression. Forty-nine of the patients showed follicular lymphoma. A high expression of bcl-2 was found in 93%, high expression of p53 in 57%, and low expression of Ki-67 in 96%. Follicular lymphoma grade III showed a p53 expression (p = 0.07) slightly higher than follicular lymphoma grades I and II, not reaching statistical significance. Follicular lymphoma grades I and II tended to express lower Ki-67 and higher levels of bcl-2 expression than grade III (p = 0.06). Fifty-five cases showed diffuse large-B-cell lymphoma. Among them, bcl-2 was absent in 39%, whereas p53 and Ki-67 expression were high in 38%. In the diffuse large-B-cell lymphomas, a high bcl-2 expression correlated with stages III and IV (p = 0.03) and involvement of more than one extranodal area (p = 0.03). High Ki-67 expression was also associated to extranodal involvement of more than one area (p = 0.03). Overall survival of patients did not show statistically significant differences regarding Ki-67, bcl-2, and p53 tumoral expression. Prognostic factors for overall survival in the multivariate analysis were age (p = 0.02) and LDH (p = 0.003). Time to progression was worse among follicular lymphoma with high p53 expression than with mild/moderate p53 expression (p = 0.009).

Cyclin D3 immunoreactivity in follicular lymphoma is independent of the t(6;14)(p21.1;q32.3) translocation or cyclin D3 gene amplification and is correlated with histologic grade and Ki‐67 labeling index

“…Germinal centers are mostly composed by cells actively proliferating in response to antigen receptor stimulation and expressing Ki-67. 36 Likewise, in keeping with previous data, 37 we documented that grade III FLs show a high Ki-67 LI, and that cyclin D3 and Ki-67 are colocalized in most of the FL cells. Since cyclin D3 is capable of promoting cell cycle progression, 1 these findings lead to the speculation that its expression may contribute to drive proliferation in normal and neoplastic follicular cells.…”

Primary breast diffuse large B-cell lymphoma shows a non-germinal center B-cell phenotype

“…MIB-1 index has a relationship to prognosis in B-cell lymphomas. [30][31][32] The MIB-1 index in the other extranodal sites, those of DLBCL with MALT-type lymphoma in the stomach and of DLBCL in the CNS were reported to be 51 and 50%, respectively. 33,34 These clearly indicate an exceptionally high proliferative activity in primary breast DLBCL that may account for the high recurrence rate in stage IE disease.…”

Bcl-2 protein expression is the strongest independent prognostic factor of survival in primary cutaneous large B-cell lymphomas

“…Whereas some of these studies, including fewer than 65 patients, led to negative results, [37][38][39][40] more powerful analyses of more than 150 patients found that bcl-2 protein overexpression was independently related to relapse, 29 disease-free survival, 30,31 or overall survival. 32 In view of recent in vitro studies in human leukemia cell lines, 41,42 it has been suspected that a high bcl-2 expression may confer resistance to several antineoplastic agents.…”