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

Pediatric Blood and Cancer - Tập 65 Số 11 - 2018
А. Е. Druy1,2, Egor Shorikov3, Grigory Tsaur4,5,2, А. М. Попов1, A. N. Zaychikov5, С. Н. Тупоногов5, Leonid Saveliev5,2, Godelieve A.M. Tytgat6,7,8, Л. Г. Фечина6,5
1Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
2Research Institute of Medical Cell Technologies, Yekaterinburg, Russian Federation
3PET-Technology Center of Nuclear Medicine, Yekaterinburg, Russian Federation
4Department of Immunochemistry, Ural Federal University named after the First President of Russia B.N. Yeltsin, Yekaterinburg, Russian Federation
5Regional Children's Hospital N1, Yekaterinburg, Russian Federation
6Both are senior authors of the manuscript.
7Department of Pediatric Oncology, Emma Children’s Hospital (EKZ/AMC), Amsterdam, The Netherlands
8Princess Máxima Centre for Pediatric Oncology (PMC), Utrecht, The Netherlands

Tóm tắt

AbstractBackgroundDetection 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.MethodsExpression 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.ResultsNeither 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).ConclusionPHOX2B 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.

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Pediatric Blood and Cancer

Tập 65 Số 11

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