Abstract: Objective： To evaluate the relationship between WWOX expressions at the protein level and the clinic-pathological characteristics of human breast cancer. Method： Expression of WWOX was determined by immunohistochemical staining in a total of 155 tissue micro-arrays including 56 normal breast tissues, 12 ductal carcinoma in situ cases and 87 primary invasive breast carcinoma specimens. Results： A decreased or lost of WWOX expression was observed more frequently in invasive tumors (62.1%) when compared with normal breast tissues (28.6%) (P＜0.01). 82.1% of ER（-）cases and 52.5% of ER（+）cases showed a decrease or lost of WWOX expression(P＜0.05). 22.4% of premenopausal cases were completely negative for WWOX expression versus 51.8% for postmenopausal breast carcinomas (P＜0.05). Furthermore, 23.1% of stage Ⅰ (6/26), 28.6% of stage Ⅱ (10/35), and 46.2% of stage Ⅲ (12/26) tumors showed a negative WWOX protein expression (P＜0.01). Conclusions： Loss of WWOX is a common event in breast cancer. Associations of WWOX expression with ER status, menopausal status and clinical stage of the disease strengthen the hypothesis that WWOX plays a role in carcinogenesis and development of breast cancer in a pathway or pathways associated with sex steroid metabolism.

Key words: Breast neoplasms, Genes, WWOX, Estrogen receptor, Menopausal statusWWOX