BACKGROUND: This study sought to investigate biological/clinicopathological characteristics of neuroblastoma, undifferentiated subtype (NBUD). METHODS: This study examined 157 NBUD cases filed at the Children's Oncology Group Neuroblastoma Pathology Reference Laboratory, and survival rates of the patients were analyzed with known prognostic factors. Immunostainings for MYCN and MYC protein were performed on 68 tumors. RESULTS: NBUD cases had a poor prognosis (48.4% ± 5.0% 3-year event-free survival [EFS]; 56.5% ± 5.0% overall survival [OS]), and were often associated with high mitosis-karyorrhexis index (MKI, 65%), prominent nucleoli (PN, 83%), ≥ 18 months of age (75%), MYCN amplification (MYCN-A, 83%), diploid pattern (63%), and 1pLOH (loss of heterozygosity (72%). However, these prognostic indicators, except for MYCN status, had no significant impact on survival. Surprisingly, EFS for patients with MYCN-A tumors (53.4% ± 5.6%) was significantly better (P=.0248) than for patients with MYCN-nonamplified (MYCN-NA) tumors (31.7% ± 11.7%), with MYCN-NA and PN (+) tumors having the worst prognosis (9.3% ± 8.8%, P=.0045). Immunohistochemically, MYCN expression was found in 42 of 48 MYCN-A tumors. In contrast, MYC expression was almost exclusively found in the MYCN-NA tumors (9 of 20) especially when they had PN (8 of 11). Those patients with only MYC-positive tumors had the worst EFS (N=8, 12.5% ± 11.7%) compared with only MYCN-positive (N=39, 49.9% ± 17.7%) and both negative tumors (N=15, 70.0% ± 17.1%) (P= .0029). High MKI was often found in only MYCN-positive (30 of 38) but rarely in only MYC-positive (2 of 8) tumors. CONCLUSIONS: NBUD represents a unique subtype of neuroblastoma associated with a poor prognosis. In this subtype, MYC protein expression may be a new prognostic factor indicating more aggressive clinical behavior than MYCN amplification and subsequent MYCN protein expression.
BACKGROUND: This study sought to investigate biological/clinicopathological characteristics of neuroblastoma, undifferentiated subtype (NBUD). METHODS: This study examined 157 NBUD cases filed at the Children's Oncology Group Neuroblastoma Pathology Reference Laboratory, and survival rates of the patients were analyzed with known prognostic factors. Immunostainings for MYCN and MYC protein were performed on 68 tumors. RESULTS: NBUD cases had a poor prognosis (48.4% ± 5.0% 3-year event-free survival [EFS]; 56.5% ± 5.0% overall survival [OS]), and were often associated with high mitosis-karyorrhexis index (MKI, 65%), prominent nucleoli (PN, 83%), ≥ 18 months of age (75%), MYCN amplification (MYCN-A, 83%), diploid pattern (63%), and 1pLOH (loss of heterozygosity (72%). However, these prognostic indicators, except for MYCN status, had no significant impact on survival. Surprisingly, EFS for patients with MYCN-A tumors (53.4% ± 5.6%) was significantly better (P=.0248) than for patients with MYCN-nonamplified (MYCN-NA) tumors (31.7% ± 11.7%), with MYCN-NA and PN (+) tumors having the worst prognosis (9.3% ± 8.8%, P=.0045). Immunohistochemically, MYCN expression was found in 42 of 48 MYCN-A tumors. In contrast, MYC expression was almost exclusively found in the MYCN-NA tumors (9 of 20) especially when they had PN (8 of 11). Those patients with only MYC-positive tumors had the worst EFS (N=8, 12.5% ± 11.7%) compared with only MYCN-positive (N=39, 49.9% ± 17.7%) and both negative tumors (N=15, 70.0% ± 17.1%) (P= .0029). High MKI was often found in only MYCN-positive (30 of 38) but rarely in only MYC-positive (2 of 8) tumors. CONCLUSIONS: NBUD represents a unique subtype of neuroblastoma associated with a poor prognosis. In this subtype, MYC protein expression may be a new prognostic factor indicating more aggressive clinical behavior than MYCN amplification and subsequent MYCN protein expression.
Authors: S Goto; S Umehara; R B Gerbing; D O Stram; G M Brodeur; R C Seeger; J N Lukens; K K Matthay; H Shimada Journal: Cancer Date: 2001-11-15 Impact factor: 6.860
Authors: M A Grotzer; M D Hogarty; A J Janss; X Liu; H Zhao; A Eggert; L N Sutton; L B Rorke; G M Brodeur; P C Phillips Journal: Clin Cancer Res Date: 2001-08 Impact factor: 12.531
Authors: Tamás Tornóczky; Endre Kálmán; Pál G Kajtár; Tibor Nyári; Andrew D J Pearson; Deborah A Tweddle; Julian Board; Hiroyuki Shimada Journal: Cancer Date: 2004-01-15 Impact factor: 6.860
Authors: R Peto; M C Pike; P Armitage; N E Breslow; D R Cox; S V Howard; N Mantel; K McPherson; J Peto; P G Smith Journal: Br J Cancer Date: 1977-01 Impact factor: 7.640
Authors: M Khalid Khan Niazi; Jonathan H Chung; Katherine J Heaton-Johnson; Daniel Martinez; Raquel Castellanos; Meredith S Irwin; Stephen R Master; Bruce R Pawel; Metin N Gurcan; Daniel A Weiser Journal: Pediatr Dev Pathol Date: 2017-04-18
Authors: Justin Chen; Christopher S Hackett; Shile Zhang; Young K Song; Robert J A Bell; Annette M Molinaro; David A Quigley; Allan Balmain; Jun S Song; Joseph F Costello; W Clay Gustafson; Terry Van Dyke; Pui-Yan Kwok; Javed Khan; William A Weiss Journal: Cancer Discov Date: 2015-01-30 Impact factor: 39.397
Authors: Steven G DuBois; Yael P Mosse; Elizabeth Fox; Rachel A Kudgus; Joel M Reid; Renee McGovern; Susan Groshen; Rochelle Bagatell; John M Maris; Clare J Twist; Kelly Goldsmith; M Meaghan Granger; Brian Weiss; Julie R Park; Margaret E Macy; Susan L Cohn; Greg Yanik; Lars M Wagner; Randall Hawkins; Jesse Courtier; Hollie Lai; Fariba Goodarzian; Hiroyuki Shimada; Najee Boucher; Scarlett Czarnecki; Chunqiao Luo; Denice Tsao-Wei; Katherine K Matthay; Araz Marachelian Journal: Clin Cancer Res Date: 2018-08-09 Impact factor: 12.531
Authors: Mark W Zimmerman; Yu Liu; Shuning He; Adam D Durbin; Brian J Abraham; John Easton; Ying Shao; Beisi Xu; Shizhen Zhu; Xiaoling Zhang; Zhaodong Li; Nina Weichert-Leahey; Richard A Young; Jinghui Zhang; A Thomas Look Journal: Cancer Discov Date: 2017-12-28 Impact factor: 39.397
Authors: Laura Kerosuo; Pushpa Neppala; Jenny Hsin; Sofie Mohlin; Felipe Monteleone Vieceli; Zsofia Török; Anni Laine; Jukka Westermarck; Marianne E Bronner Journal: Proc Natl Acad Sci U S A Date: 2018-07-18 Impact factor: 11.205
Authors: Jordan S Taylor; Lingdao Sha; Naohiko Ikegaki; Jasmine Zeki; Ryan Deaton; Jamie Harris; Jeannine Coburn; Burcin Yavuz; Amit Sethi; Hiroyuki Shimada; David L Kaplan; Peter Gann; Bill Chiu Journal: J Pediatr Surg Date: 2019-08-31 Impact factor: 2.545
Authors: Ian C MacArthur; Yi Bei; Heathcliff Dorado Garcia; Michael V Ortiz; Joern Toedling; Filippos Klironomos; Jana Rolff; Angelika Eggert; Johannes H Schulte; Alex Kentsis; Anton G Henssen Journal: JCI Insight Date: 2019-04-18
Authors: Risa Teshiba; Shinya Kawano; Larry L Wang; Lejian He; Arlene Naranjo; Wendy B London; Robert C Seeger; Julie M Gastier-Foster; A Thomas Look; Michael D Hogarty; Susan L Cohn; John M Maris; Julie R Park; Hiroyuki Shimada Journal: Pediatr Dev Pathol Date: 2014-09-10