Open AccessReg IV is an independent prognostic factor for relapse in patients with clinically localized prostate cancer
Author(s) -
Ohara Shinya,
Oue Naohide,
Matsubara Akio,
Mita Koji,
Hasegawa Yasuhisa,
Hayashi Tetsutaro,
Usui Tsuguru,
Amatya Vishwa Jeet,
Takeshima Yukio,
Kuniyasu Hiroki,
Yasui Wataru
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.00846.x
Subject(s) - chromogranin a , medicine , prostate cancer , immunostaining , neuroendocrine differentiation , immunohistochemistry , prostatectomy , cancer , univariate analysis , pathology , prostate specific antigen , biochemical recurrence , proportional hazards model , oncology , multivariate analysis
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. ( Cancer Sci 2008; 99: 1570–1577)