Immunohistochemical detection of p140trkA and p75LNGFR neurotrophin receptors in neuroblastoma.
In neuroblastoma, high levels of mRNA for p140trkA and p75LNGFR neurotrophin receptors are predictive of favorable outcome. Their evaluation by Northern blot, however, requires substantial amounts of tissue and this prevents their routine evaluation as well as the possibility for multicenter studies to be easily carried out. In an attempt to overcome these limitations, the feasibility and reliability of determining both neurotrophin receptors on cryostat sections by immunohistochemistry were assessed, and these findings were compared to those obtained from Northern blot analysis. Primary tumor samples from 28 untreated patients at all stages were evaluated by using H10 anti-p140trkA and ME20.4 anti-p75LNGFR mAbs. Although weak, positive immunostaining was found in 9 of 28 tumors for p140trkA and in 5 of 28 tumors for p75LNGFR. As compared to Northern blot, the concordance rate was 79% (22 of 28 cases) for p140trkA (p < 0.05) and 71% (20 of 28 cases) for p75LNGFR (p < 0.05). No case negative for Northern blot was found to be positive with immunohistochemistry. Since only high mRNA levels for both receptors have been shown to be clinically relevant, their immunohistochemical detection, although less sensitive than Northern blot, can be just as sufficient and reliable as a prognostic tool, and possibly with a better cost-benefit ratio.
Dominici
C
C
Department of Pediatrics, University La Sapienza, Rome, Italy.
Nicotra
M R
MR
Alemà
S
S
Bosman
C
C
Castello
M A
MA
Donfrancesco
A
A
Gallo
P
P
McDowell
H
H
Natali
P G
PG
D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D002648:Child; D006801:Humans; D007150:Immunohistochemistry; D009447:Neuroblastoma / Q000175:diagnosis; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000737:chemistry
D000911:Antibodies, Monoclonal; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA