Prospective investigation of applicability and the prognostic significance of bone marrow involvement in patients with neuroblastoma detected by quantitative reverse transcription PCR.

Autor: Druy AE; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation.; Research Institute of Medical Cell Technologies, Yekaterinburg, Russian Federation., Shorikov EV; PET-Technology Center of Nuclear Medicine, Yekaterinburg, Russian Federation., Tsaur GA; Research Institute of Medical Cell Technologies, Yekaterinburg, Russian Federation.; Regional Children's Hospital N1, Yekaterinburg, Russian Federation.; Department of Immunochemistry, Ural Federal University named after the First President of Russia B.N. Yeltsin, Yekaterinburg, Russian Federation., Popov AM; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Zaychikov AN; Regional Children's Hospital N1, Yekaterinburg, Russian Federation., Tuponogov SN; Regional Children's Hospital N1, Yekaterinburg, Russian Federation., Saveliev LI; Research Institute of Medical Cell Technologies, Yekaterinburg, Russian Federation.; Regional Children's Hospital N1, Yekaterinburg, Russian Federation., Tytgat GAM; Department of Pediatric Oncology, Emma Children's Hospital (EKZ/AMC), Amsterdam, The Netherlands.; Princess Máxima Centre for Pediatric Oncology (PMC), Utrecht, The Netherlands., Fechina LG; Regional Children's Hospital N1, Yekaterinburg, Russian Federation.
Jazyk: angličtina
Zdroj: Pediatric blood & cancer [Pediatr Blood Cancer] 2018 Nov; Vol. 65 (11), pp. e27354. Date of Electronic Publication: 2018 Jul 14.
DOI: 10.1002/pbc.27354
Abstrakt: Background: Detection of bone marrow (BM) involvement in patients with neuroblastoma is crucial for staging and defining prognosis. Furthermore, the persistence of residual tumor cells in the BM is associated with an unfavorable outcome.
Methods: Expression of PHOX2B, TH, ELAVL4, and B4GALNT1 (GD2-synthase) was analyzed by quantitative polymerase chain reaction in neuroblastoma cell lines, control BM samples, and in BM samples from patients. The threshold level of expression for each gene was established through receiver operator characteristic analysis and used to determine the diagnostic test performance. The prognostic significance of BM involvement was assessed by survival rates calculations. The median of follow-up time was 36.1 months.
Results: Neither PHOX2B nor TH expression was detected in control BM, while expression of ELAVL4 was found in 20 (76.9%) and GD2-synthase in 15 (57.7%) of 26 samples. The overall correct predictive value for TH, ELAVL4, and GD2-synthase, based on thresholds levels, was 0.952, 0.828, and 0.767, respectively, whereas the overall correct predictive value for PHOX2B was 0.994. The PHOX2B/TH expression in diagnostic BM of patients with neuroblastoma corresponded with a decreased survival rate (P < 0.001) in the total cohort and in different risk groups. Predominance of normalized expression of PHOX2B over TH > 1.68 in the diagnostic BM samples demonstrated an adverse prognostic effect (P = 0.006). Persistence of PHOX2B/TH expression in the BM during and after induction chemotherapy resulted in dismal outcome (P = 0.022 and P = 0.012).
Conclusion: PHOX2B and TH are the most optimal markers for detection of BM involvement, allowing identification of high-risk patients. Predominance of PHOX2B expression over TH has a strong adverse prognostic impact.
(© 2018 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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