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.
OBJECTIVE
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.


RESULTS
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].


CONCLUSIONS
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.
Paik
J H
JH
Department of Pathology and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Jeon
Y K
YK
Park
S S
SS
Kim
Y A
YA
Kim
J E
JE
Huh
J
J
Lee
S-S
SS
Kim
W H
WH
Kim
C W
CW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D002648:Child; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D018858:Germinal Center / Q000737:chemistry / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D025803:Tumor Suppressor Protein p14ARF / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27