Journal List > Korean J Hematol > v.42(2) > 1032712

Kim, Sohn, Kim, Lee, Kang, and Chae: The Expression of p16 in Diffuse Large B-cell Lymphoma and Its Prognostic Implications

Abstract

Background:

The molecular mechanisms that are responsible for the initiation and progression of diffuse large B-cell lymphoma are largely unknown. p16 is an inhibitor of cyclin-dependent kinase and its inactivation by methylation has been reported as a major tumorigenic mechanism in malignant tumors. The aim of this study was to analyze the correlation between the clinical data and the p16 protein expression in diffuse large B-cell lymphomas.

Methods:

Tumor samples were obtained from 62 patients who were suffering with diffuse large B-cell lymphoma. To investigate the role of p16 in the pathogenesis and progression of diffuse large B-cell lymphoma, 62 cases of diffuse large B-cell lymphoma were examined for their expression of p16 via performing immunohistochemistry. The correlation of the p16 expression with the various clinicopathologic findings was also analyzed.

Results:

p16 was expressed in all the cases of reactive lymphoid hyperplasia (100%) and in 40 cases (64.5%) out of the 62 cases of diffuse large B-cell lymphoma that we studied. The expression rate of p16 was 31.8% in the high risk group and 82.5% in the low risk group of diffuse large B-cell lymphoma. The expression rate of p16 in the fatal cases was 12.5%. For our results, the loss of a p16 expression in diffuse large B-cell lymphoma was noted, and especially in the high risk group (P=0.04).

Conclusion:

The loss of p16 appeared to be involved in the genesis or progression of diffuse large B-cell lymphoma. In addition, the loss of the p16 expression may play important roles for patients' progression into the high risk group and it may cause more mortality for those patients with diffuse large B-cell lymphoma. Deranged expressions and loss of the p16 expression may play an important role in the pathogenesis of diffuse large B-cell lymphoma.

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Fig. 1
(A, B) The microscopic morphology of diffuse large B-cell lymphoma. The tumor is composed of medium-sized to large lymphoid cells with oval to round, vesicular nuclei with fine chromatin and membrane bound nucleoli (H&E stain, A: ×200, B: ×400). (C, D) Immunostaining for p16 in low-risk group (C) and in the case of high-risk group (D) of diffuse large B-cell lymphoma. p16 is strongly expressed in the nuclei of low-risk group (C), whereas high-risk group diffuse large B-cell lymphoma cells are weakly expressed in the nuclei (D).
kjh-42-129f1.tif
Fig. 2
Kaplan-Meier survival curve stratified according to the extent of p16. When the expression of p16 is stratified as 10% or more (n=40) and below 10% (n=22), the survival curve of p16 shows no significance.
kjh-42-129f2.tif
Table 1.
Clinical data of 62 cases with diffuse large B-ce lymphoma
Sex  Male   30
   Female   32
Age (yr) 33∼94 (median, 59)
Clinical follow-up duration (months) 5∼140 (median, 76)
Response to chemotherapy
   Complete remission 26 (41.9%)
   Partial remission 16 (25.8%)
   Stable disease 12 (19.4%)
   Progressive disease 8 (12.9%)
Ann Arbor stage I 5 (8.1%)
  II 11 (17.7%)
  III 12 (19.4%)
  IV 26 (41.9%)
  Undeterm ined 8 (12.9%)
Table 2.
Patient characteristics of high and low risk group according to the International Prognostic Index
  High-risk group (22 patients) Low-risk group (40 patients)
Age (yr) 44∼94 33∼85
  Median 66 50
  >60 years 13/22 (59.1%) 17/40 (42.5%)
LDH increase 15/22 (68.2%) 19/40 (47.5%)
Bone marrow involvement 9/22 (40.9%) 0/40 (0%)
Stage III/IV 17/22 (77.3%) 18/40 (45.0%)
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