Endothelin-1 in human prostatic carcinoma treated with androgen withdrawal: an immunohistochemical study.
BACKGROUND
Various reports suggest a role for endothelin-1 in prostatic carcinoma. The objective of the current study was to evaluate the changes of the immunodetectable endothelin-1 in prostatic carcinomas characterized by different grades of regression due to total androgen withdrawal.


METHODS
An immunohistochemical study was made on eleven prostatic carcinomas treated with neoadjuvant hormonal therapy for 3 months, followed by radical prostatectomy. Another ten specimens of untreated carcinomas were studied for comparison. An appraisal of androgen receptors was associated. A highly specific polyclonal antibody against endothelin-1 and a commercial monoclonal mouse antibody for androgenic receptors were used.


RESULTS
In all cases, a prevalent quantity of androgenic receptor-positive tumor cells were present. Neoplastic cells of untreated carcinomas showed a strong and heterogeneous staining for endothelin -1. In unregressed areas of treated cases, the features of endothelin-1 and androgen-receptor staining were the same as those of untreated cases. In areas characterized by moderate histologic regression, the endothelin-1 staining became more heterogeneous. In areas of strong histologic regression, a diffuse membrane staining was often noted. Only in completely regressed cancer cells was a definite loss of immunodetectable endothelin-1 and androgenic receptors observed.


CONCLUSIONS
Endothelin-1 is one of the proteins intrinsic to prostatic epithelial cells, both benign and malignant. In cases treated with androgen withdrawal, histologic regression is not uniform. In unmodified areas, immunodetectable endothelin-1 and androgenic receptors also are unmodified, thus suggesting some mechanism that substitutes for the action of androgen. Only neoplastic cells with complete histologic regression also lose androgenic receptors and endothelin-1, whereas the preserved immunostaining in deeply modified prostatic neoplastic cells seems to indicate that these cells still are potentially active.
de Matteis
A
A
Department of Experimental Medicine and Pathology, "La Sapienza" University of Rome, Rome, Italy.
Guidi
A
A
Di Paolo
B
B
Franco
G
G
Revoltella
R P
RP
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D017373:Cyproterone Acetate / Q000627:therapeutic use; D019332:Endothelin-1 / Q000378:metabolism*; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D007124:Immunoenzyme Techniques; D016729:Leuprolide / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D019332:Endothelin-1; D011944:Receptors, Androgen; D017273:Goserelin; D017373:Cyproterone Acetate; D016729:Leuprolide