Reg IV is an independent prognostic factor for relapse in patients with clinically localized prostate cancer.
Regenerating islet-derived family, member 4 (REG4, which encodes Reg IV) is a candidate marker for cancer and inflammatory bowel disease. We investigated the potential prognostic role of Reg IV immunostaining in clinically localized prostate cancer (PCa) after radical prostatectomy. Immunohistochemical staining of Reg IV was performed in 98 clinically localized PCa tumors obtained during curative radical prostatectomy. Intestinal and neuroendocrine differentiation was investigated by MUC2 and chromogranin A immunostaining, respectively. The prognostic significance of immunohistochemical staining for these factors on prostate-specific antigen (PSA)-associated recurrence was assessed by Kaplan-Meier analysis and a Cox regression model. Phosphorylation of the epidermal growth factor receptor (EGFR) by Reg IV was analyzed by Western blot. In total, 14 (14%) of the 98 PCa cases were positive for Reg IV staining. Reg IV positivity was observed frequently in association with MUC2 (P = 0.0182) and chromogranin A positivity (P = 0.0012). Univariate analysis revealed that Reg IV staining (P = 0.0004), chromogranin A staining (P = 0.0494), Gleason score (P < 0.0001) and preoperative PSA concentration (P = 0.0167) were significant prognostic factors for relapse-free survival. Multivariate analysis indicated that Reg IV staining (P = 0.0312), Gleason score (P = 0.0014) and preoperative PSA concentration (P = 0.0357) were independent predictors of relapse-free survival. In the LNCaP cell line, EGFR phosphorylation was induced by the addition of Reg IV-conditioned medium. These results suggest that Reg IV expression is an independent prognostic indicator of relapse after radical prostatectomy.
Ohara
Shinya
S
Department of Molecular Pathology, Hiroshima Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Oue
Naohide
N
Matsubara
Akio
A
Mita
Koji
K
Hasegawa
Yasuhisa
Y
Hayashi
Tetsutaro
T
Usui
Tsuguru
T
Amatya
Vishwa Jeet
VJ
Takeshima
Yukio
Y
Kuniyasu
Hiroki
H
Yasui
Wataru
W