No Influence of bcl-2, p53, and p21 waf1 Protein Expression on the Outcome of Pediatric Hodgkin Lymphomas

Abstract

In Argentina, lymphomas account for 13.6% of all pediatric tumors and 47% of them are Hodgkin lymphoma. Previous studies of lymphoma series have reported the expression of apoptotic and cell cycle proteins. Our aim was to study these markers in our pediatric patients and correlate them with their outcome. Immunohistochemical staining with monoclonal antibodies anti-p53, bcl-2, p21, and mdm2 were performed on formalin-fixed paraffin-embedded Hodgkin lymphoma lymph node biopsies from 54 pediatric patients. The analyzed oncogenes p53, bcl-2, p21, and mdm2 exhibited 81%, 44%, 76%, and 90% positive staining, respectively. The most prevalent p53/p21 expression pattern was p53+/p21+, in 57% of cases, whereas concerning p53/mdm2 expression pattern p53+/mdm2+ was observed in 61% of cases. We failed to find any statistically significant correlation between oncogene expression and patient's survival. It seems that p53 plays an important role in lymphomagenesis in our studied population, because it is overexpressed in 81% of Hodgkin lymphoma cases and in more than 50% of cases, it might be able to activate its cellular effectors. Bcl-2 staining observed in 44% of our cases could represent a failure in bcl-2 down-regulation that leads to a rescue event in defective germinal center B-cells, that allows them to develop into Reed-Sternberg and Hodgkin cells.

Histology of pediatric classic Hodgkin lymphoma: From diagnosis to prognostic stratification

“…Literature data on BCA are focused mainly on CD20 and correlate its expression to either worse, 40 neutral, 41,42 or better 43 survival rates compared with controls. The same holds true for Bcl2 and p53, which have been variably associated with prognosis 10,20,43‐49 . It is nonetheless noteworthy that the only available studies on pediatric populations are in line with our results, as they exclude any prognostic role for such markers 10,20 …”

“…Bcl2 was scored as positive if >10% of HRS cells had protein expression equal to or greater than the accompanying small lymphocytes 19 . p53 was scored as positive if >50% of neoplastic cells featured strong nuclear staining 20 . Immunohistochemical reactions were independently assessed by two pathologists (MP and ST), with excellent interobserver agreement ( k > 0.80).…”

“…19 p53 was scored as positive if >50% of neoplastic cells featured strong nuclear staining. 20 Immunohistochemical reactions were independently assessed by two pathologists (MP and ST), with excellent interobserver agreement (k > 0.80). In discrepant cases, consensus was reached after joint sessions at the microscope.…”

Pediatric Hodgkin lymphoma- biomarkers, drugs, and clinical trials for translational science and medicine

“…Approximately 50% of pediatric HL patients express Bcl-2 [36], and this Bcl-2 positivity is associated with decreased EFS in low-risk patients, and unfavorable risk patients in multivariate analysis [36]. However, some reports suggested that Bcl-2 expression did not affect outcomes [24, 37], and thus the prognostic value of Bcl-2 expression in HL is unclear.…”

Prognostic impact of CD15 expression and proliferative index in the outcome of children with classical Hodgkin lymphoma

“…CD15 negativity was observed in 33.8% of the cases and no association with clinical presentation or survival (OS, 95% CD15+ and CD15−; FFS, 82% CD15+ vs. 80% CD15−) was found. Dinand et al 1 also found that CD15 negativity was associated with p53 negativity ( P = 0.009), leading them to suggest that CD15 expression would relate to H‐RS cell survival and that “p53 deregulation might have a role in the loss of CD15 antigen expression.” This statement is difficult to interpret, since it is accepted that detection, and not absence of p53 immunoexpression, indicates p53 deregulation 9. Moreover, no information on the percentage of tumor cells expressing p53 used to define positive and negative cases (cut‐off), was provided; the use of different cut‐off criteria is a recognized cause of the controversy about the prognostic value of p53 expression in different HL studies 10.…”