Expression of p75(LNGFR) and Trk neurotrophin receptors in normal and neoplastic human prostate.
OBJECTIVE
To analyse the occurrence and cell distribution of p75(LNGFR) and Trk neurotrophin receptors in normal prostate, benign prostatic hypertrophy (BPH) and prostate carcinoma, and to determine the effect of androgen suppression on the expression of these proteins in prostate cancer samples.


METHODS
The study comprised formalin-fixed and paraffin-embedded material, obtained during surgery and from cadavers during removal of organs for transplantation. Light microscopy immunohistochemistry was carried out using polyclonal antibodies against Trks, and a monoclonal antibody against p75(LNGFR). General markers for epithelial and endocrine cells were assessed in parallel.


RESULTS
TrkA immunoreactivity (IR) was restricted to the basal epithelial cells in some acini (37%). This pattern remained unchanged or IR extended to the whole acini in BPH, and varied widely in prostate cancer. In normal tissue and BPH, TrkC IR was detected exclusively in the stroma. Nevertheless, it progressively increased in the epithelial cells of well-differentiated to moderately differentiated prostate carcinoma, whereas in stromal cells there were no substantial changes. TrkB IR was absent in all the samples. There was weak p75(LNGFR) IR in normal epithelial cells, which increased in prostate cancer and to a lesser extent in BPH. Androgen suppression was ineffective in reversing TrkA modifications, whereas it caused a decrease in the expression of TrkC and p75(LNGFR).


CONCLUSIONS
The abnormal growth of prostatic epithelium is accompanied by increased TrkA expression and the induction of TrkC expression in epithelial cells. These results suggest that neurotrophins could be involved in the abnormal growth of the human prostate, acting through specific Trk signal-transducing receptors whose expression is regulated by androgens.
Guate
J L
JL
Servicios de Urología Hospital San Agustín, Avilés; Departamentos de Cirugía y Especialidades Médico-Quirúrgicas. Madrid, Spain.
Fernández
N
N
Lanzas
J M
JM
Escaf
S
S
Vega
J A
JA
D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism; D008297:Male; D011467:Prostate / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D020917:Receptor, trkA / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*
D053379:Chromogranin A; D002864:Chromogranins; D017475:Receptors, Nerve Growth Factor; D007633:Keratins; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA