{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:05:56Z","timestamp":1790640356513,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pathology International"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:p>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\u2010appropriate tumor differentiation\/maturation, is common in infants and has mutual interaction with Schwann cells via the <jats:italic>NGF\/NTRK1<\/jats:italic> pathway and gain of whole chromosome 17. In contrast, UH is prevalent in older children and is molecularly heterogeneous. <jats:italic>MYCN<\/jats:italic> amplification is the most frequent genomic abnormality in tumors with UH. <jats:italic>MYCN<\/jats:italic>\u2010amplified tumors demonstrate characteristic histology, the same as MYC\u2010positive neuroblastoma. Chromosome 1pLOH is often associated with <jats:italic>MYCN<\/jats:italic> amplification, but on the other hand, chromosome 11qLOH rarely occurs in combination with <jats:italic>MYCN<\/jats:italic> amplification. 11qLOH has an inferior prognostic impact in UH without <jats:italic>MYCN<\/jats:italic> amplification. The high expression of ALK protein is a negative prognostic factor in both <jats:italic>ALK<\/jats:italic> 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 <jats:italic>ATRX<\/jats:italic> 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.<\/jats:p>","DOI":"10.1111\/pin.13085","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T21:38:08Z","timestamp":1614807488000},"page":"232-244","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Biological categories of neuroblastoma based on the international neuroblastoma pathology classification for treatment stratification"],"prefix":"10.1111","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9008-4281","authenticated-orcid":false,"given":"Atsuko","family":"Nakazawa","sequence":"first","affiliation":[{"name":"Department of Clinical Research Saitama Children's Medical Center, Saitama  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19990715)86:2<349::AID-CNCR20>3.0.CO;2-Y"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19990715)86:2<364::AID-CNCR21>3.0.CO;2-7"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/73.2.405"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11773"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.28251"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20000901)89:5<1150::AID-CNCR25>3.0.CO;2-7"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.29848"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.2350\/06-06-0117.1"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24779"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-018-0098-6"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2611"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20557"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20011115)92:10<2699::AID-CNCR1624>3.0.CO;2-A"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202750"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevOncog.v5.i1.30"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/87.19.1470"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20717"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20005"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605014"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.2350\/08-12-0579.1"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24238"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210661"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.0630"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.12665"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1991.9.4.581"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07399"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07398"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07261"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07397"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.12.003"},{"key":"e_1_2_13_32_1","first-page":"131","volume-title":"Neuroblastoma","author":"Kushner BH","year":"2005"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.22495"},{"key":"e_1_2_13_34_1","unstructured":"NakazawaA UryuK HagaCet al. \u2009A High ALK Expression is Associated with an Unfavorable Histology in Neuroblastoma. 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