Reevaluation of trkA expression as a biological marker of neuroblastoma by high-sensitivity expression analysis--a study of 106 primary neuroblastomas treated in a single institute.
OBJECTIVE
It has previously been shown that neuroblastomas with favorable prognosis often express a high level of nerve growth factor receptor trkA. We performed an expression analysis of trkA in 106 NB samples based on the quantitative real-time polymerase chain reaction (PCR) and reevaluated the prognostic power of trkA.


METHODS
A total of 106 primary tumors from NB patients treated from 1988 to 2009 were analyzed. MYCN was amplified in 13 cases. TaqMan probe method was used for quantitative PCR. Primers and probes were designed to detect trkA I and trkA II, but not the oncogenic splice variant trkA III.


RESULTS
Expression analysis by real-time PCR revealed a wide range of expression levels of trkA within neuroblastoma tissues. Extremely low levels of trkA that were undetectable by semiquantitative PCR were able to be quantified by this method. trkA was predominantly expressed in tumors with favorable outcome. Further analysis of trkA expression was performed in a cohort excluding mass-screened neuroblastomas. Strikingly, multivariate analysis containing age, MYCN status, and trkA expression identified trkA as the only variable that independently predicts the prognosis of the 44 patients who presented clinically.


CONCLUSIONS
High-resolution expression analysis targeting trkA and trkA II may add more statistical power on trkA as a biological marker.
Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba 260-8677, Japan. hishiki@faculty.chiba-u.jp
Tomoro
T
Hishiki
Takeshi
T
Saito
Keita
K
Terui
Yoshiharu
Y
Sato
Ayako
A
Takenouchi
Eriko
E
Yahata
Sachie
S
Ono
Akira
A
Nakagawara
Takehiko
T
Kamijo
Yohko
Y
Nakamura
Tadashi
T
Matsunaga
Hideo
H
Yoshida
D000367:Age Factors; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D007223:Infant; D007564:Japan / Q000453:epidemiology; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011003:Ploidies; D011379:Prognosis; D020917:Receptor, trkA / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D020917:Receptor, trkA