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Biological categories of neuroblastoma based on the international neuroblastoma pathology classification for treatment stratification
Author(s) -
Nakazawa Atsuko
Publication year - 2021
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/pin.13085
Subject(s) - atrx , neuroblastoma , histology , telomere , biology , immunohistochemistry , cancer research , telomerase , pathology , phenotype , medicine , mutation , gene , genetics , cell culture
The International Neuroblastoma Pathology Classification (INPC), which distinguishes a favorable histology (FH) and an unfavorable histology (UH), is one of the most powerful prognostic factors in patients with neuroblastoma. FH that shows spontaneous regression or age‐appropriate tumor differentiation/maturation, is common in infants and has mutual interaction with Schwann cells via the NGF/NTRK1 pathway and gain of whole chromosome 17. In contrast, UH is prevalent in older children and is molecularly heterogeneous. MYCN amplification is the most frequent genomic abnormality in tumors with UH. MYCN ‐amplified tumors demonstrate characteristic histology, the same as MYC‐positive neuroblastoma. Chromosome 1pLOH is often associated with MYCN amplification, but on the other hand, chromosome 11qLOH rarely occurs in combination with MYCN amplification. 11qLOH has an inferior prognostic impact in UH without MYCN amplification. The high expression of ALK protein is a negative prognostic factor in both ALK mutated or amplified tumors and FH, but not in UH. Abnormal maintenance/elongation of telomeres; overexpression of telomerase reverse transcriptase (TERT) and the alternative lengthening of telomeres (ALT) phenotype due to ATRX mutation, are another molecular event in UH. The INPC, incorporating immunohistochemistry for MYCN, MYC, ALK, TERT and ATRX, represents a practical and implementable approach to create the biological category for the future management of patients with this unique disease.