TrkA expression in peripheral neuroblastic tumors: prognostic significance and biological relevance.
BACKGROUND
This study was conducted to investigate the prognostic significance and biologic relevance of trkA expression levels in peripheral neuroblastic tumors (pNTs) (i.e., neuroblastoma, ganglioneuroblastoma, and ganglioneuroma).


METHODS
Levels of trkA expression from a total of 265 pNTs were determined by quantitative polymerase chain reaction analysis with Genescan software. The results were analyzed according to histopathology (favorable histology [FH] vs. unfavorable histology [UH] according to the International Neuroblastoma Pathology Classification) and MYCN tumor status (amplified vs. nonamplified) along with clinical stage and outcomes of the patients.


RESULTS
The levels of trkA expression differed significantly between the group of patients who were alive and well (n = 170 patients) and the group that had progressed or died (n = 95 patients) and between the group that was alive (n = 188 patients) and the group that died (n = 77 patients). However, the trkA expression levels were not independent predictors of clinical outcome when the proportional hazards model contained the known prognostic variables of clinical stage, histopathology, and MYCN status (all tests were done in 196 patients). In the neuroblastoma category (n = 173 tumors), tumors in the FH/nonamplified MYCN subset (n = 112 tumors) expressed higher levels of trkA and showed an age-dependent neuroblastic differentiation: They were classified into either a poorly differentiated subtype (n = 91 tumors; all patients age < 1.5 years at diagnosis) or a differentiating subtype (n = 21 tumors; 57% of patients ages 1.5-5.0 years). Tumors in the UH/amplified MYCN subset (n = 30 tumors) expressed significantly lower levels of trkA and showed very limited neuroblastic differentiation. Tumors in the FH/amplified MYCN subset were very rare (n = 3 tumors) and expressed higher levels of trkA. Tumors in the UH/nonamplified MYCN subset (n = 28 tumors) had trkA levels in a wide range and showed limited neuroblastic differentiation.


CONCLUSIONS
For patients with pNTs, levels of trkA expression did not add significant information to prognostic grouping, as defined by the combination of clinical stage, histopathology, and MYCN status. There was a biologically relevant correlation between molecular properties (trkA expression and MYCN status) and histopathologic features of the tumors in the neuroblastoma category.
Shimada
Hiroyuki
H
Department of Pathology and Laboratory Medicine, Childrens Hospital Los Angeles and University of Southern California Keck School of Medicine, Los Angeles, California 90027, USA. hshimada@chla.usc.edu
Nakagawa
Atsuko
A
Peters
Julius
J
Wang
Hong
H
Wakamatsu
Peter K
PK
Lukens
John N
JN
Matthay
Katherine K
KK
Siegel
Stuart E
SE
Seeger
Robert C
RC
D014408:Biomarkers, Tumor / Q000032:analysis; D002454:Cell Differentiation; D002675:Child, Preschool; D005260:Female; D018305:Ganglioneuroblastoma / Q000235:genetics* / Q000473:pathology; D005729:Ganglioneuroma / Q000235:genetics* / Q000473:pathology; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger; D020917:Receptor, trkA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D020917:Receptor, trkA