Usefulness of Tyrosine Hydroxylase mRNA for Diagnosis and Detection of Minimal Residual Disease in Neuroblastoma

Rie Ito; Satoru Asami; Shigeki Kagawa; Shigeyasu Motohashi; Hiroyuki Shichino; Motoaki Chin; Yukihiro Yoshida; Norimichi Nemoto; Hideo Mugishima; Takashi Suzuki

doi:10.1248/bpb.27.315

Regular Articles

Usefulness of Tyrosine Hydroxylase mRNA for Diagnosis and Detection of Minimal Residual Disease in Neuroblastoma

Rie Ito, Satoru Asami, Shigeki Kagawa, Shigeyasu Motohashi, Hiroyuki Shichino, Motoaki Chin, Yukihiro Yoshida, Norimichi Nemoto, Hideo Mugishima, Takashi Suzuki

Author information

Rie Ito
Clinical Pharmacy, College of Pharmacy, Nihon University
Satoru Asami
Clinical Pharmacy, College of Pharmacy, Nihon University
Shigeki Kagawa
Clinical Pharmacy, College of Pharmacy, Nihon University
Shigeyasu Motohashi
Chemistry, College of Pharmacy, Nihon University
Hiroyuki Shichino
Department of Pediatrics, School of Medicine, Nihon University
Motoaki Chin
Department of Pediatrics, School of Medicine, Nihon University
Yukihiro Yoshida
Department of Orthopedics, School of Medicine, Nihon University
Norimichi Nemoto
Department of Pathology, School of Medicine, Nihon University
Hideo Mugishima
Department of Pediatrics, School of Medicine, Nihon University
Department of Advanced Medicine, Division of Cell Regeneration and Transplantation, School of Medicine, Nihon University
Takashi Suzuki
Clinical Pharmacy, College of Pharmacy, Nihon University
Department of Pediatrics, School of Medicine, Nihon University

Keywords: neuroblastoma, tyrosine hydroxylase, hematopoietic stem cell transplantation, minimal residual disease, reverse transcription polymerase chain reaction

JOURNAL FREE ACCESS

2004 Volume 27 Issue 3 Pages 315-318

DOI https://doi.org/10.1248/bpb.27.315

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Abstract

Neuroblastoma (NB) is the most common malignant solid tumor in childhood and, among all childhood malignancies, is second only to leukemia. NB originates before birth in the neural crest, which develops into the adrenal medullae and sympathetic ganglia. In the adrenal medulla, tyrosine hydroxylase (TH) is the first enzyme in the pathway of catecholamine synthesis. We used reverse transcription polymerase chain reaction (RT-PCR) to examine the expression of TH mRNA in NB and Ewing's sarcoma cell lines, small round cell tumors (SRCTs) containing NB, and other clinical tumor samples (osteosarcoma, osteochondroma, and Wilms' tumor). In total, we analyzed 33 clinical tumor samples. TH mRNA was expressed in all three NB cell lines examined, but not in two ES cell lines or in a breast cancer cell line. We detected TH mRNA in 23 of 25 NB tumor samples (92%), but in none of the SRCTs or other clinical tumor samples. This RT-PCR technique showed a sensitivity for TH mRNA of one NB cell per 10⁵ negative cells. Based on these results, the detection of TH mRNA is very useful both as a tumor marker for NB and for detecting minimal residual disease. Therefore, we can use this method to detect tumor cell contamination before hematopoietic stem cell transplantation.

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