Expression of p53, c-Myc, or Bcl-6 Suggests a Poor Prognosis in Primary Central Nervous System Diffuse Large B-Cell Lymphoma Among Immunocompetent Individuals

Abstract

Context.—Primary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) in immunocompetent individuals, although rare, has been rising in incidence. Currently, no reliable prognostic markers are available for these individuals. Objective.—To study the implications of expression of a panel of oncogenic proteins (Bcl-2, Bcl-6, and c-Myc) and p53 for predicting clinical outcome, particularly overall survival, in immunocompetent individuals with primary CNS DLBCL. Design.—Fourteen primary CNS DLBCL cases were retrospectively studied by immunohistochemistry on formalin-fixed, paraffin-embedded sections for the expression of c-Myc, Bcl-2, Bcl-6, and p53. Results.—The overall frequencies of expression for p53, c-Myc, Bcl-2, and Bcl-6 in these cases were 29%, 50%, 71%, and 57%, respectively. Cases with expression of p53, c-Myc, or Bcl-6 had a poorer overall survival than those without (Kaplan-Meier survival analysis: 50% cumulative overall survival, 2 months vs 30–60 months, P = .02, log-rank test; 9–16 months vs 21–60 months, P = .03, log-rank test; and 9–16 months vs 21–60 months, P = .16, log-rank test, respectively). The expression of Bcl-2 or proliferation activity by MIB-1 showed no correlation with overall survival. Likewise, the clinical parameters, including age, location of tumors, multiplicity of tumor lesions, and lactase dehydrogenase levels revealed no impact on overall survival. Conclusion.—Our results suggest that patients with expression of p53, c-Myc, or Bcl-6 have a poorer overall survival than those without. Since traditional prognostic markers in non-CNS DLBCL, such as staging and International Prognostic Index scores, are not applicable to primary CNS DLBCL, evaluation of p53, c-Myc, and Bcl-6 by immunohistochemistry may be warranted as part of prognostic evaluation in immunocompetent patients with primary CNS DLBCL. Further studies are indicated to confirm our observations.

Elevated expression of transforming acidic coiled‐coil‐containing protein 3 (TACC3) reflects aggressiveness of primary central nervous system lymphomas

“…Although many markers and clinical factors have been studied to elucidate their prognostic significance, the usefulness of biological markers for PCNSLs are controversial. [23][24][25][26][27] For example, Chang et al reported that patients who express p53, c-Myc or Bcl-6 in tumor cells have poorer overall survival. 23 Nozaki et al noted that immunostaining of p53 detects an alteration that occurs in over one-third of PCNSLs.…”

“…[23][24][25][26][27] For example, Chang et al reported that patients who express p53, c-Myc or Bcl-6 in tumor cells have poorer overall survival. 23 Nozaki et al noted that immunostaining of p53 detects an alteration that occurs in over one-third of PCNSLs. 24 They also commented that although it's not always the case, p53 protein expression in nuclei reflects p53 mutation.…”

“…The nuclear staining was regarded as positive for p53 and Ki-67 based on previous studies. 23,26,27 The ratios of p53 and Ki-67 positive tumor cells were calculated in three randomly selected high-power fields. The samples were classified into high and low labeling index (cut off value, 23% and 33%, respectively) based on the median value.…”

“…To the best of our knowledge, although several biological markers of PCNSLs have been suggested, their prognostic value is controversial. [23][24][25][26][27] Therefore, we examined TACC3 expression in PCNSLs using immunohistochemical techniques, and statistically analyzed the relationship between TACC3 expression and clinicopathological features, as well as patient prognosis.…”

“…However, a lack of biological markers and understanding of the exact mechanisms of PCNSLs makes it difficult to diagnose and stratify their treatment. To the best of our knowledge, although several biological markers of PCNSLs have been suggested, their prognostic value is controversial 23–27 …”