Advanced Pathology Classification Toward Precision Stratification of Neuroblastic Tumors

The International Neuroblastoma Pathology Classification (INPC) distinguishing Favorable Histology (FH) and Unfavorable Histology (UH) Group has been providing invaluable information in determining the prognosis and therapy stratification of the neuroblastoma patients. While survival of the FH patients is excellent, that of the UH patients currently remains around 40–50%. These observations are prompting us to seek immunohistochemical biomarkers tightly associated with aggressive tumor progression within the UH Group. Toward this goal, neuroblastoma pathology research needs to shift its gear to the direction from identifying “Prognostic Factors” to defining “Actionable/Druggable” targets based on the concept of “Precision Medicine.” Our recent studies define MYC-driven neuroblastoma and suggest that MYC-family (MYCN/MYC) proteins are such “Actionable/Druggable” targets. Furthermore, telomerase overexpression and ALT phenotype due to ATRX/DAXX loss, both are immunohistochemically detectable, would also likely be additional “Actionable/Druggable” biomarkers of highly aggressive neuroblastomas. For this reason, future INPC should incorporate immunohistochemical detection of these markers.