Aberrant expression of CARM1, a transcriptional coactivator of androgen receptor, in the development of prostate carcinoma and androgen-independent status.
BACKGROUND
Coactivator-associated arginine methyltransferase 1 (CARM1) is a transcriptional coactivator of the androgen receptor (AR). It is involved in the regulation of the biologic functions of the AR. It remains to be determined whether CARM1 is involved in prostatic carcinogenesis.


METHODS
The expression of CARM1 in normal prostate epithelium, high-grade prostatic intraepithelial neoplasia (PIN), and prostate carcinoma tissue was examined in 66 previously untreated patients with prostate carcinomas, as well as 12 patients with hormone-independent prostate carcinoma, using immunohistochemical methods.


RESULTS
Cell staining was observed in the cytoplasm and the nucleus. In 66 patients without previous hormonal treatment, the percentage of cells that stained positively for CARM1 in benign prostate tissue specimens (mean values: cytoplasm, 23%; nucleus, 16%) was statistically significantly less than the percentage of positively stained cells in PIN (mean values: cytoplasm, 56%; nucleus, 30%; P < 0.001) and in prostatic adenocarcinoma specimens (mean values: cytoplasm, 79%; nucleus, 53%; P < 0.001). The difference between adenocarcinoma and PIN also was statistically significant (P < 0.001). The staining intensity for CARM1 was significantly lower in benign prostate tissue specimens compared with PIN and prostatic adenocarcinoma specimens (P < 0.001). In the 12 patients with androgen-independent prostatic adenocarcinoma, the expression of CARM1 was significantly increased when compared with patients without previous hormonal treatment. Expression of CARM1 was not correlated with age, Gleason score sum, pathologic stage, lymph node metastasis, extraprostatic extension, surgical margin status, vascular invasion, or perineural invasion.


CONCLUSIONS
The authors found that overexpression of CARM1 was involved in the development of prostate carcinoma as well as androgen-independent prostate carcinoma. Since CARM1 is functionally different from most other transcriptional coactivators of the AR, it may serve as a new target for the treatment of hormone-independent prostate carcinoma.
Hong
Heng
H
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, University Hospital 3465, University Medical Center, 550 North University Boulevard, Indianapolis, IN 46202, USA.
Kao
Chinghai
C
Jeng
Meei-Huey
MH
Eble
John N
JN
Koch
Michael O
MO
Gardner
Thomas A
TA
Zhang
Shaobo
S
Li
Lang
L
Pan
Chong-Xian
CX
Hu
Zhiqiang
Z
MacLennan
Gregory T
GT
Cheng
Liang
L
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011484:Protein-Arginine N-Methyltransferases / Q000096:biosynthesis*; D011944:Receptors, Androgen / Q000378:metabolism*
D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1