Measurement of tyrosine hydroxylase transcripts in bone marrow using biopsied tissue instead of aspirates for neuroblastoma.
BACKGROUND
Molecular detection of tyrosine hydroxylase (TH) transcripts by quantitative RT-PCR (qRT-PCR) is a sensitive method to detect neuroblastoma (NB) cells in the bone marrow (BM). However, its clinical utility following chemotherapy has not been thoroughly investigated.


METHODS
TH transcripts in the BM were measured by qRT-PCR both at diagnosis and during the course of chemotherapy. The results were analyzed with respect to assay timing, tumor volume and histological findings.


RESULTS
TH transcripts were detected in 100% of BM aspirates at diagnosis in cases with concurrent tumor involvement in the BM section; however, the proportion of TH transcript positive BM aspirates in cases with concurrent tumor involvement in the BM section gradually decreased following chemotherapy (55.5% after three cycles, 28.6% after six cycles and 0% after nine or more cycles of chemotherapy). Decreased proportion of TH transcript positive BM aspirates was associated with reduced tumor volume in the BM and differentiation of tumors into mature forms during chemotherapy. When qRT-PCR was performed with both aspirated and biopsied tissue during chemotherapy, TH transcripts were detected in BM tissue not only in all of the histology-positive cases but also in some of the histology-negative cases, while the proportion of TH transcript positive BM aspirates was low, even in histology-positive cases.


CONCLUSIONS
Measurement of TH transcripts in BM aspirates does not appear to be clinically useful during or after chemotherapy. Therefore, molecular monitoring of NB cells during or after chemotherapy using BM tissue is more optimal than testing on BM aspirates.
Lee
Seung-Tae
ST
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Suh
Yeon Lim
YL
Ko
Young-Hyeh
YH
Ki
Chang-Seok
CS
Sung
Ki Woong
KW
Kim
Hee-Jin
HJ
Kim
Jong-Won
JW
Kim
Sun-Hee
SH
Chueh
Heewon
H
Lee
Soo Hyun
SH
Yoo
Keon Hee
KH
Koo
Hong Hoe
HH
D000293:Adolescent; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001706:Biopsy / Q000379:methods / Q000592:standards; D001856:Bone Marrow Examination / Q000379:methods* / Q000592:standards; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009447:Neuroblastoma / Q000188:drug therapy / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis* / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase