title: Clinical application of minimal residual neuroblastoma cell detection by reverse transcriptase-polymerase chain reaction.
abstract: The highly sensitive method to detect neuroblastoma (NB) cells using reverse transcriptase polymerase chain reaction (RT-PCR) was applied in the practical clinics, and its efficacy was assessed in the present study. Human tyrosine hydroxylase (TH), a rate-limiting enzyme in the catecholamine biosynthesis, was used as the marker for NB cells, and the expression of THmRNA was examined in 13 samples (four peripheral blood and nine bone marrow) harvested from seven patients (four with stage IV, one with stage III, two with stage II) using RT-PCR with our original primers. The positive signals for NB cells were detected in four samples (one peripheral blood and three bone marrow) by the PCR method, but were undetectable by the conventional histological examinations. In the present series, a case that showed a positive signal for NB cells in the peripheral blood showed a remarkably unfavorable clinical course, indicating that the circulating NB cells detected by the PCR method can be a sign of the progressively advanced NB, and may define a new prognostic factor suggesting higher risk. In another case, the PCR detection for the residual NB cells in the bone marrow provided important supporting evidence to determine the necessity of the additional chemotherapy and the suitable timing for bone marrow transplantation. This detection also guaranteed the safety of the bone marrow for transplantation. The PCR method was considered to be very beneficial in the selected cases. However, some problems such as the false-negative results in the negative urinary vanillylmandelic acid secretor were also highlighted in the present study.
authors.affiliation: Department of Surgery, National Children's Hospital, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kuroda
authors.forename: M
authors.initials: M
authors.lastname: Saeki
authors.forename: M
authors.initials: M
authors.lastname: Nakano
authors.forename: S
authors.initials: S
authors.lastname: Mizutani
mesh_terms: D019797:3-Iodobenzylguanidine; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood / Q000235:genetics; D001853:Bone Marrow / Q000473:pathology; D016026:Bone Marrow Transplantation; D002648:Child; D005188:False Negative Reactions; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D009447:Neuroblastoma / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012194:RNA-Directed DNA Polymerase; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000097:blood / Q000235:genetics; D014642:Vanilmandelic Acid / Q000652:urine
chemical_list: D014408:Biomarkers, Tumor; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D012333:RNA, Messenger; D019797:3-Iodobenzylguanidine; D014642:Vanilmandelic Acid; D014446:Tyrosine 3-Monooxygenase; D012194:RNA-Directed DNA Polymerase