Immunohistochemical expression of endothelin-1 and endothelin-A and endothelin-B receptors in high-grade prostatic intraepithelial neoplasia and prostate cancer.
OBJECTIVE
To analyze the expression of endothelin-1 (ET-1), endothelin-A receptor (ET-A-R), and endothelin-B receptor (ET-B-R) in incidental prostate cancer in cystoprostatectomies (CyPs), clinically detected hormonally untreated and hormonally treated prostate cancer in radical prostatectomies (RPs), and hormone-independent prostate cancer in transurethral resections of the prostate (TURPs). High-grade prostatic intraepithelial neoplasia (HGPIN) was also investigated.


METHODS
Nineteen CyPs and 44 RPs (25 untreated, 19 treated) with pT2a Gleason score 6 cancer and HGPIN were examined. The study included 9 TURPs with hormone-independent cancer and 8 normal cases from CyPs without prostate cancer and HGPIN. ET-1, ET-A-R, ET-B-R, and the proliferation marker Ki67 were investigated immunohistochemically.


RESULTS
The mean proportion of prostate cancer cells with strong ET-1, ET-A-R, and ET-B-R expression in CyPs was lower (18.5%, 28.0%, and 14.7%, respectively) than in the untreated group (40.7%, 39.7%, and 25.1%) and higher than in treated group (5.0%, 13.9%, and 11.3%). The highest values were in the hormone-independent cancer group (53.9%, 48.9%, 33.3%). The trend in the proportion of HGPIN cells overexpressing ET-1, ET-A-R, and ET-B-R was similar to that in the cancer groups. The values in HGPIN lesions were always slightly greater than those in the cancers. Ki67 expression in HGPIN and prostate cancer in CyPs was lower than in RPs and TURPs.


CONCLUSIONS
Our study showed for the first time that ET-1, ET-A-R, and ET-B-R expression is not limited to the late prostate cancer phases. It is also seen in HGPIN as well as in prostate cancers considered to be clinically insignificant, such as those seen in CyP specimens. Although the series of cases in each group was small, our data may have clinical significance.
Montironi
Rodolfo
R
Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, Ancona, Italy. r.montironi@univpm.it
Mazzucchelli
Roberta
R
Barbisan
Francesca
F
Stramazzotti
Daniela
D
Santinelli
Alfredo
A
Lòpez Beltran
Antonio
A
Cheng
Liang
L
Montorsi
Francesco
F
Scarpelli
Marina
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019332:Endothelin-1 / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D019048:Prostatic Intraepithelial Neoplasia / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000737:chemistry*; D044022:Receptor, Endothelin A / Q000032:analysis*; D044023:Receptor, Endothelin B / Q000032:analysis*
D019332:Endothelin-1; D019394:Ki-67 Antigen; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B