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. Copyright 2001 American Cancer Society.
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. Copyright 2001 American Cancer Society.
Authors: Juan Juan Yin; Khalid S Mohammad; Sanna M Käkönen; Stephen Harris; J Ruth Wu-Wong; Jerry L Wessale; Robert J Padley; I Ross Garrett; John M Chirgwin; Theresa A Guise Journal: Proc Natl Acad Sci U S A Date: 2003-08-26 Impact factor: 11.205