The Relationship Between Apoptotic Activity and Prognostic Factors in Neuroblastomas

Prognostic parameters in determining risk groups for treatment in neuroblastoma are cellular differentiation, mitosis karyorrhexis index (MKI), N-myc amplification and age. However, additional prognosticators are still needed because patients can show unpredictable biological behavior. We aimed to study the prognostic significance of apoptotic activity in neuroblastomas.

Thirty-five primary neuroblastoma were evaluated. The data including stage, treatment protocol, metastatic disease, survival, N-myc status, age and prognostic categorization were obtained from the clinical records. The differentiation and MKI were evaluated in hematoxylin and eosin stained slides. Apoptotic activity was assessed by both bcl-2 immunohistochemical staining and the transferase-mediated d-UTP-biotin nick end labeling (TUNEL) method. Data were correlated with established prognostic factors and clinical outcome.

Twenty-five (71.4%) cases were located in the adrenal. Sixteen cases showed low and 19 high MKI. Thirty-three (%94) were immunopositive for bcl-2. TUNEL staining was negative in 2 cases. Of the remaining positive 33 cases, 14 had an apoptotic index of ≤2%, 11 of 2-4% and 8 of ≥4%. Cases located in the adrenal showed higher scores of bcl-2 positivity than extra-adrenal tumors. There was no statistical significance for both bcl-2 staining and apoptotic index in correlation with cellular differentiation, MKI, N-myc amplification, age and other clinical parameters. Statistical significance was observed between bcl-2 scoring and tumor localization.

According to our results, apoptotic activity is unlikely to be a prognostic parameter in neuroblastomas. Some studies showing significant correlations between clinical outcome and both bcl-2 immunoscoring and apoptotic index, as assessed by the TUNEL method, differences in case numbers and methodology can explain these conflicting results. Larger series and different methodologies are needed to evaluate the prognostic value of apoptotic activity in neuroblastomas.