Immunohistochemical expression of P53 protein in nephroblastoma: a predictor of unfavorable prognosis

Abstract

Objective Immunohistochemical expression of P53 protein is so closely related to status of mutation of P53 gene which is tightly linked with pathogenesis of nephroblastoma or Wilms tumor. This study aims to determine the immunohistochemical expression of P53 protein and its predictors in formalin-fixed paraffin-embedded tissue blocks of patients with nephroblastoma. Materials and methods A series of 83 histologically diagnosed cases of nephroblastoma from formalin-fixed paraffin-embedded tissue blocks archived at the Department of Pathology, Makerere University, in Kampala, Uganda, were analyzed. Monoclonal anti-p53 antibody (DO-7, DAKO) was used to assess the expression of P53 protein expression. Multivariable logistic regression analysis was performed to determine the predictors of P53 protein immunohistochemical expression, and statistical significance was considered when p-value was less than 0.05. Results Most (42.2%, n = 35) of the cases were in advanced tumor stages (III–V), and almost one-quarter (21.7%, n = 18) of the cases were in high-risk group. The immunohistochemical expression of P53 protein was (8.4%, n = 7), and there were more (83.3%, n = 5) positive anaplastic cases for P53 protein compared with (2.6%, n = 2) of P53 expression for non-anaplastic cases. High risk (AOR = 3.42, 95% CI = 7.91–12.55, p = 0.037) and anaplasia (AOR = 1.41, 95% CI = 13.85–4.46, p = 0.001) were potential predictors of immunohistochemical expression of P53 protein. Conclusion Most of patients with nephroblastoma in resources-limited settings are diagnosed with advanced clinical stages. Association of P53 protein with anaplasia found in this study indicates the possibility of having novel target therapy for treatment of patients with anaplastic form of nephroblastoma with a focus of identifying molecules that lead to its suppression in such subpopulations of patients with nephroblastoma.

High Expression of WT1 and Low Expression of p53 in Archived Blocks of Children with Wilms Tumor in South Western Uganda

“…The low prevalence (5.88%) of anaplasia is similar to findings by Dome et al, Morgan et al, and Murphy of 7.2% and 13%, respectively. 6 , 18 , 21 The similarity can be explained by the fact that all these were laboratory studies and involved a review of tissue blocks similar to what we did. However, this is lower than the 63% and 24.39% reported by Okello et al and Ekuk et al, respectively.…”

“…The low expression of p53 (13%) is similar to findings from India of 9.7% and 16.0%, 16.7% from Nigeria studies, and 8.4% in Uganda by Morgan. 16 , 18 , 23 , 24 All these studies involved the review of histology slides similar to what we did. The similarity between Nigeria and Uganda studies can also be explained by the similarity in participants’ clinical characteristics.…”

“…The 20% positivity of TP53 in anaplastic tumors is also lower than the 83.3% reported by Morgan at Makerere histopathology laboratory. 18 The lack of statistically significant association between p53 and histologic features can be explained by the fact that most cases had mixed-type histology which virtually does not express p53. 28 …”