REG1A Expression is an Independent Factor Predictive of Poor Prognosis in Patients with Breast Cancer Yasuhiro Sasaki, MD, Yoshihiro Minamiya, MD, PhD, Naoko Takahashi, Taku Nakagawa, MD, PhD, Yoshihisa Katayose, MD, PhD, Aki Ito, MD, Hajime Saito, MD, PhD, Satoru Motoyama, MD, PhD, and Jun-ichi Ogawa, MD, PhD Department of Surgery, Akita University School of Medicine, 1-1-1 Hondo, Akita City 010-8543, Japan Background: Regenerating gene I alpha (REG1A) is a growth factor known to affect pancreatic islet b cells. Although REG1A expression has also been observed in various malignant tumors, the correlation between REG1A expression and the clinicopathological characteristics of breast cancer and patient prognosis has not been evaluated. Methods: Resected breast cancer tissues obtained at surgery from 150 breast cancer patients was stained with anti-REG1A antibody, after which the relative area occupied by stained tumor cells was evaluated under a light microscope and correlated with known clinicopath- ological factors. Results: Whereas tumor cells were frequently stained with anti-REG1A antibody, cells from normal breast tissue were not stained. REG1A expression in tumors of breast cancer patients with HER2-positive disease was higher than those with HER2-negative disease (P = .0009). The 10-year disease-specific survival rate among patients with lower levels of REG1A was significantly better than among those with higher levels (P = .0002 by log rank test). Multivariate Cox proportional hazard analyses revealed REG1A (hazard ratio, 2.07; 95% confidence interval, 1.93 to 11.29; P = .0005) and axillary lymph node status (hazard ratio, 4.44; 95% confidence interval, 1.52 to 11.29; P = .0003) to be independent factors affecting the 10-year disease-specific survival rate. Conclusion: High levels of REG1A expression within tumors are an independent predictor of poor prognosis in patients with breast cancer. Breast cancer is the most commonly occurring malignancy among women in the Western world, and approximately 30% of breast cancer patients even- tually experience a fatal recurrence after apparently successful treatment. 1,2 In recent years, more effective adjuvant therapies that make use of anticancer and antimolecular drugs and that are designed on the basis of pathological malignancy grade, stage and molecular status, drug sensitivity and/or gene analy- sis have come into common use. 3–8 However, it re- mains difficult to identify high-risk patients likely to experience relapse after surgery and adjuvant ther- apy. Additional prognostic indicators able to distin- guish among such patients would therefore be highly desirable. Regenerating gene (REG) was first identified through screening a regenerating pancreatic islet-de- rived cDNA library taken from a 90% depancre- atized rat. 9 It is now known that the REG gene family is composed of various acute phase reactants, lectins, antiapoptotic factors, and growth factors affecting pancreatic islet cells, neural cells, and epithelial cells within the digestive system. 10,11 To date, 17 REG family genes have been identified, 12 including two Published online September 10, 2008. Address correspondence and reprint requests to: Yoshihiro Minamiya, MD, PhD; E-mail: minamiya@med.akita-u.ac.jp Published by Springer Science+BusinessMedia, LLC Ó 2008 The Society of Surgical Oncology, Inc. Annals of Surgical Oncology 15(11):3244–3251 DOI: 10.1245/s10434-008-0137-2 3244