Expression and prognostic implications of cell cycle regulatory molecules, p16, p21, p27, p14 and p53 in germinal centre and non‐germinal centre B‐like diffuse large B‐cell lymphomas

Abstract

To evaluate the different expression patterns and the prognostic significance of cell cycle regulatory molecules in diffuse large B-cell lymphomas (DLBCLs) of germinal centre (GC) and non-GC phenotypes. Tissue microarray slides composed of 126 extranodal and 88 nodal DLBCLs were immunostained for p16, p21, p27, p14 and p53. DLBCLs were classified into GC and non-GC phenotype according to the immunohistochemical expression of bcl-6, CD10, and MUM1. Aberrant expression of p53 was more frequent in the GC phenotype in nodal cases (P = 0.038), and the loss of p16, p21 and p14 expression was significantly more common in the non-GC phenotype (P = 0.004, P = 0.001, P < 0.001). Concurrent disruptions of the p16-Rb and p14-p53 pathways as represented by the immunoprofile of p16/p14/p53 (-/-/+) were associated with a poor prognosis in the GC phenotype [mean survival 31 months in the p16/p14/p53 (-/-/+) group versus 62 months in the other groups, P =0.0485]. The expression and prognostic implications of cell cycle regulatory molecules differ between GC and non-GC phenotypes in DLBCLs. The immunoprofile of p16/p14/p53 (-/-/+) within the GC phenotype of DLBCLs can be defined as a poor prognostic subgroup.