Immunohistochemical and angiogenetic features of nephroblastoma in children and their prognostic significance

Abstract

Relevance. Nephroblastoma is the most common malignant tumor of the kidneys in children and is characterized by pronounced morphological and biological polymorphism. Determination of the expression of immunohistochemical (IHC) markers p53, Ki-67 and CD34 has high diagnostic and prognostic significance, allowing to assess the proliferative activity, apoptotic resistance and angiogenetic potential of the tumor. In the conditions of Uzbekistan, systemic studies of these markers in children with nephroblastoma were limited, which determines the relevance of this work. Purpose of the study. To evaluate the relationship between the expression of IHC markers p53, Ki-67 and CD34 with morphological features, stage of the disease, frequency of relapses and metastasis in children with nephroblastoma who received complex treatment followed by radiation therapy. Materials and methods. A retrospective study of 230 children with morphologically verified nephroblastoma observed in 2012–2021 was conducted. IHC analysis was performed using monoclonal antibodies to p53, Ki-67, and CD34 (DAKO, Denmark). Expression levels (high, moderate, low) were determined and compared with the clinical stage (SIOP), degree of differentiation (G1–G4), frequency of relapses, and distant metastases. Statistical analysis was performed using the χ² test at a significance level of p<0.05. Results and discussion. High expression of p53 was detected in 10.0% of patients, mainly at stages III–IV and low differentiation (G3–G4), associated with an increased risk of relapses (82.6%) and metastases (82.6%) (p<0.001). Ki-67>60% was found in 10.4% of cases, mainly in aggressive morphotypes, and also correlated with the frequency of relapses (83.3%) and metastases (79.2%) (p<0.001). High expression of CD34 (12.2%) reflected enhanced angiogenesis and was accompanied by a high level of metastatic lesions (67.9%) (p<0.001). In 40-50% of cases, data on markers were missing, which is associated with insufficient standardization of IHC diagnostics. Conclusion. p53, Ki-67 and CD34 are independent unfavorable prognostic markers in children with nephroblastoma, reflecting a high potential for tumor aggression.

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