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Overexpression of HRad17 mRNA in Human Breast Cancer: Correlation with Lymph Node Metastasis

Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu 874-0838, Japan [A. K., N. S., M. M.]; Kimmel Cancer Institute, Jefferson Medical College, Philadelphia, Pennsylvania 19107 [K. M.]; Department of Surgery, Oita Prefectural Hospital, Oita 870-8511, Japan [H. U.]; Division of Digestive Disease and Nutrition, University of Massachusetts Medical Center, Worcester, Massachusetts 01655 [G. F. B.]; Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115 [D. A., L. B. C.]; and Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan [K. S.]

Purpose: A novel human gene, designated HRad17, was identified as the human homologue of the Rad17 of Schizosaccharomyces pombe and Rad24 of Saccharomyces cerevisiae. In yeast, these genes play a critical role in maintaining genomic stability. The aim of this study was to evaluate the expression of HRad17 in human breast cancer.

Experimental Design: We investigated HRad17 mRNA expression in 64 cases of human breast cancer by means of reverse-transcription-PCR, in situ hybridization, and immunohistochemistry.

Results: The HRad17 mRNA was overexpressed in 35 cases (54.7%). Twenty-four (68.6%) of 35 cases with HRad17 overexpression in cancer tissues were node-positive, whereas only 8 (27.6%) of 29 cases without HRad17 overexpressions were node-positive. The expression of HRad17 mRNA correlated with both lymph node metastasis (P = 0.001) and high Ki67 labeling index (P = 0.006). Although not significantly different, expression of HRad17 mRNA tended to correlate with tumor size (P = 0.06) and expression of mutant p53 protein (P = 0.10). Furthermore, expression of HRad17 mRNA was an independent predictor of axillary lymph node metastasis as well as of lymphatic permeation by multivariate analysis (P < 0.0001).

Conclusions: Our study demonstrates that HRad17 might be related to the development of lymph node metastasis in human breast cancers. Although its function still remains unclear, the expression of HRad17 mRNA could open up a new window for the diagnostic staging and treatment of human breast cancers.