乳腺癌组织WWOX基因表达及其与ER、绝经状态的相关性

目的：探讨WWOX基因在乳腺癌组织中的表达及其与雌激素受体(estrogen receptor, ER)、绝经状态等临床病理学特征的关系。方法：应用免疫组织化学SP法检测56例正常乳腺组织、12例乳腺导管原位癌和87例侵袭性乳腺癌组织WWOX蛋白的表达，结合临床病理学资料进行分析。结果：62.1%(54/87)的乳腺癌组织和28.6%（16/56）正常乳腺组织中出现WWOX蛋白表达降低或丢失，两组间差异有统计学意义（P＜0.01 ）。50%的乳腺导管原位癌组织中WWOX 蛋白表达降低。82.1% 的ER（-）组和 52.5% ER（+）组病例表现为WWOX蛋白表达降低或缺失，差异有统计学意义(P＜0.05)。51.8%的绝经后患者和22.4%的绝经前患者出现WWOX表达完全缺失，两组间差异有统计学意义(P＜0.05)。此外，晚期乳腺癌患者WWOX表达降低或缺失的比例增高，Ⅰ、Ⅱ、Ⅲ期患者中WWOX表达完全缺失的比例分别为23.1%、28.6%和46.2%，各期间的差异有统计学意义（P＜0.01）。结论:乳腺癌中存在着WWOX基因的表达缺失，其异常表达与ER状态、绝经状态和肿瘤临床分期关系密切，提示WWOX基因可能是通过激素受体信号途径在乳腺癌的发生和发展中发挥作用。

Expression of WWOX in tissues of breast cancer and its association with ER and menopausal status

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.