Endothelin-1 in human prostatic carcinoma treated with androgen withdrawal

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Abstract
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. Cancer 2001;91:1933–9. © 2001 American Cancer Society.