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. MATERIALS AND 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). CONCLUSION: 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.

Neurotrophins and neurotrophin receptors in some neural crest-derived tumours (ganglioneuroma, phaeochromocytoma and paraganglioma).

AIM: This study analyses the occurrence and distribution of neurotrophins and their receptors in some types of tumours of neural-crest derived cells. METHODS AND RESULTS: Light microscopy immunohistochemistry associated with quantitative image analysis was used to study the expression of neurotrophins (nerve growth factor, brain-derived neurotrophic factor and neurotrophin (NT)-3) and their cognate receptors (p75(LNGFR), TrkA, TrkB and TrkC) in histologically defined ganglioneuroma, phaeochromocytoma and paraganglioma. The material was fixed in 10% formaldehyde, paraffin-embedded and processed for indirect peroxidase immunohistochemistry using a battery of poly- and monoclonal antibodies to detect neurotrophins and their receptors, as well as some neuronal, endocrine and glial cell markers. A subpopulation of cells in phaeochromocytomas and ganglioneuromas expressed NT-3, but not other neurotrophins, while in paragangliomas no neurotrophins were detected. Regarding neurotrophin receptors, all tumours lacked p75(LNGFR), except for the ganglionic part of a case of mixed phaeochromocytoma, whereas they displayed TrkA (two of two ganglioneuromas, six of nine phaeochomocytomas and three of four paragangliomas). Furthermore, TrkC was regularly detected in a neuronal subpopulation in ganglioneuroma. Interestingly, the percentage of neurones expressing TrkA and TrkC was increased with respect to normal tissues in ganglioneuromas, as well as the percentage of the area occupied by TrkA-immunoreactive cells in the phaeochromocytomas. CONCLUSION: The pattern of expression of neurotrophins and neurotrophin receptors in the analysed tumours basically matches that of sympathetic neurones, adrenal chromaffin cells and paraganglionic cells, and suggests responsiveness of these cells to neurotrophins. Nevertheless, the function of TrkA and TrkC in regulating the biology of these tumours, if any, remains to be elucidated.

Neuroendocrine cells in benign prostatic hyperplasia and prostatic carcinoma: effect of hormonal treatment.

The present study was undertaken to analyze the changes in neuroendocrine cells of the human prostate induced by neoplasms and the effect of hormonal treatment. Samples of human prostate (n = 47) were obtained during surgery or removal of organs for transplantation. The cases analyzed represent normal prostates (n = 4); benign prostatic hyperplasias (n = 10; prostatic carcinomas with Gleason scores of 2-4 (n = 5), 5-7 (n = 10), and 8-10 (n = 3), and prostatic carcinomas treated with hormonal therapy (n = 15). Immunohistochemistry for chromogranin A was performed, and the density of neuroendocrine cells as well as the intensity of the immunostaining within their cytoplasms were evaluated using image analysis. Neuroendocrine cells showing chromogranin A immunoreactivity were identified in all cases studied. They were localized scattered in the acini, and no differences in their morphology were observed among groups. Interestingly, chromogranin A immunoreactivity was also present in typical epithelial cells of prostatic cancer with Gleason scores ranging from 8 to 10. The density of chromogranin A immunoreactive cells was higher in neoplastic tissue with respect to the normal prostate, reaching maximal values in prostatic carcinomas with Gleason scores of 8-10 which were hormonally treated. Regarding the intensity of immunostaining in the prostatic carcinomas with Gleason scores of 8-10 only, a significant increase in relation to the other groups was found. The present results demonstrate that the neuroendocrine cells have similar morphological features and distribution in normal prostate, benign prostatic hyperplasia, and prostatic carcinoma. Their density in prostatic cancer increases following hormonal therapy and varies in relation to the tumoral degree or histological evaluation, suggesting a role of neuroendocrine cells in human prostatic cancer.

[Prospective studies for determining the duration of prevention in superficial tumors of the bladder]. / Estudio prospectivo para determinar la duracion de la profilaxis en los tumores superficiales de vejiga.

The study covers a series of 221 patients with pTa or pT1 vesical tumours who were treated by RTU and had an endovesical cytostatic agent instilled prophylactically for a year. Before beginning the tumour resection, biopsies in map with cold forceps were routinely taken from the trigone, side walls, bottom walls and vesical cup. It was decided to monitor the patients by performing cystoscopies and biopsies in map with cold forceps every quarter. During the second and third year the endoscopic and bioptic monitoring was done every six months. During the time when the cytostatic agents were instilled, a significant decrease (p less than 0.01) in the percentage of patients with 'CIS' was observed. After discontinuing the instillation, the percentage of patients with 'CIS' reversed to similar figures as seen prior to the study. It can be deduced from this observation that prophylaxis can be effective against those elements of the urothelial disease which influence the arrival of new events and the increase of the tumoral stage, and that the control of those factors disappears when the prophylaxis is discontinued. The study illustrates that prophylaxis in the urothelial disease should be maintained indefinitely.

[Carcinosarcoma and papillary transitional cell carcinoma coexisting in the same bladder]. / Carcinosarcoma y carcinoma papilar de células transicionales coexistentes en la misma vejiga.

A case of synchronically coexistent carcinosarcoma and transitional cell carcinoma, with separate neoplastic processes in the same urinary bladder is presented. This tumour association is as far as we know, the second case reported in the literature. Carcinosarcoma was formed by an epithelial component represented by a high level transitional cell carcinoma and a mesenchymal component characterized by an unspecific fusocellular sarcoma with chondrosarcomatous differentiation. An immunohistochemical analysis was performed, confirming the dual nature of the carcinosarcoma.