EBAG9/RCAS1 expression and its prognostic significance in prostatic cancer.
Estrogen receptor-binding fragment-associated gene 9 (EBAG9) has been identified as a primary estrogen-responsive gene from MCF-7 human breast cancer cells (Watanabe T, et al., Mol Cell Biol 1998;18:442-9). EBAG9 is identical with RCAS1 (receptor-binding cancer antigen expressed on SiSo cells), which has been reported as a cancer cell surface antigen implicated in immune escape (Nakashima M, et al., Nat Med 1999;5:938-42). In our present study, we examined EBAG9 expression in human prostatic tissues and investigated its prognostic significance in patients with prostatic cancer. EBAG9 expression in normal prostatic epithelial cells and PC-3, DU145 and LNCaP cancer cells was determined by Western blot analysis. Immunohistochemic analysis was performed in 21 benign and 81 malignant prostatic specimens, and patients' charts were reviewed for clinical, pathologic and survival data. EBAG9 was abundantly expressed in the prostate cancer cells compared to the normal epithelial cells. Strong and diffuse immunostaining in the cytoplasm of EBAG9 was found in 44 of 81 (54%) cancerous tissue samples. EBAG9 expression significantly correlated with advanced pathologic stages and high Gleason score (p = 0.0305 and < 0.0001, respectively). EBAG9 was more frequently expressed at sites of capsular penetration (79%) and lymph node metastasis (100%) compared to intracapsular primary tumors (54%) (p = 0.0264 and 0.0048, respectively). Positive EBAG9 immunoreactivity significantly correlated with poor PSA failure-free survival (p = 0.0059). EBAG9/RCAS1 may play a significant role in cancer progression via an immune escape system. Immunodetection of EBAG9/RCAS1 expression can be a negative prognostic indicator for patients with prostatic cancer.
Takahashi
Satoru
S
Department of Urology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. takahashi-uro@h.u-tokyo.ac.jp
Urano
Tomohiko
T
Tsuchiya
Fujiko
F
Fujimura
Tetsuya
T
Kitamura
Tadaichi
T
Ouchi
Yasuyoshi
Y
Muramatsu
Masami
M
Inoue
Satoshi
S
D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D018450:Disease Progression; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011960:Receptors, Estrogen / Q000378:metabolism; D015996:Survival Rate; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C120762:EBAG9 protein, human; D011960:Receptors, Estrogen; D017430:Prostate-Specific Antigen