GCDFP-15对乳腺癌卵巢转移的诊断价值

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目的 探讨特异性大囊肿病液体蛋白-15(gross cystic disease fluid protein-15,GCDFP-15)和mammaglobin在乳腺癌卵巢转移诊断中的价值.方法 收集1995年11月~2007年12月我院收治的4 704例乳腺癌中12例经病理证实的乳腺癌卵巢转移患者及10例乳腺和卵巢双原发癌患者的临床病理资料,以免疫组织化学法探讨最具有鉴别诊断价值的分子标志.结果 乳腺癌卵巢转移患者的中位年龄为45岁[(28~53)岁].在诊断卵巢转移之前,12例(100%)均有卵巢外转移.该病术前影像学检查阴性者为9例(75%),术前漏诊率亦高达75%.乳腺癌发生卵巢转移以双侧多见(9例),仅表现为镜下转移的占75%.乳腺癌卵巢转移患者的GCDFP-15和mammaglobin的表达较卵巢原发上皮性癌患者的高,分别是75%、0(P<0.001)和50%、0(P=0.033),差异有统计学意义.血清学检查乳腺癌卵巢转移患者和乳腺、卵巢双原发癌患者的CA153、CA125均有上升,但CA153数值无差异(128.6 u/ml vs.56.48 u/ml,P=0.315 CA125在乳腺癌卵巢转移患者轻微升高,中位数值81.88 u/ml[(47.15~966.9)u/ml],在卵巢原发癌患者中明显升高,中位数值1 073 u/ml[(134.3~1 821)u/ml],差异有统计学意义(P=0.003).结论 乳腺癌卵巢转移常见于绝经前年轻女性患者,且大部分患者在出现卵巢转移以前已经有其他部位的转移.卵巢转移病变一般非常微小,通常是镜下转移,术前容易被误诊或漏诊;免疫组织化学联合检测特异性分子GCDFP-15、mammaglobin、WT1和CA125有助于与原发性卵巢癌相鉴别,卵巢双侧病变及血清CA125的轻微上升也有助于诊断乳腺癌的卵巢转移.“,”Objective To explore the value of GCDFP-15 (gross cystic disease fluid protein-15) and mammaglobin as specific molecules involved in ovary cancer resulted from metastasis of breast cancer. Methods Data from Nov. 1995 to Dec. 2007 were undergone retrospectively analysed. Twenty patients of metastatic ovarian cancer (MOC) from breast cancer and 10 patients of primary epithelial ovarian cancer (EOC) with a history of breast cancer were obtained. Immunohistochemical method was employed to detect the more diagnostic value of the specific molecules in these patients. Results In MOC patients, the average age was 45 years old(ranged from 28 to 53 years old), 9 of the 12 cases were incidental findings at therapeutic oophorectomy. Twelve patients (100%) had extraovarian metastases at the diagnosis of ovarian metastasis. The ovaries were grossly normal in 9(75%) cases. The preoperative imaging examinations including computed tomography (CT) and ultrasonography (US) were negative in 9 patients (75%) and the diagnosis of ovarian metastasis has been neglected in 9 patients(75%) before oophorectomy. Ovarian metastases were bilateral in 81.81% patients (9/11). The positive expression of GCDFP-15 and mammaglobin protein in the tissues of MOC were significantly higher than those in the EOC (75% vs. 0,P<0.001; 50% vs. 0,P=0.033). The positive expression of WT1 and CA125 protein in the tissues of MOC were significantly lower than those in the EOC (16.66% vs. 80%, P=0.008; 16.66% vs.90%,P=0.002). Of the serum markers, the preoperative level of serum CA153 was not different between the two groups(128.6 u/ml of patients with MOC vs. 56.48 M u/ml of patients with EOC,P=0.315). The serum CA125 level rose in 50% MOC patients (6/12) with a mean value of 81.88 u/ml [(47.15~966.9)u/ml)],and in 100% EOC patients while the mean value was 1 073 u/ml [(134.3~1 821)u/ml)(P=0.003). The metastatic ovarian tumors, as measured preoperatively by ultrasonography (US) or CT, were smaller [<4 cm, (0~8.3) cm]than the primary tumors [10.2 cm, (5~26)cm](P <0.001). Bilateralism and metastases in abdominal cavity were more common among patients with MOC (P<0.001). Conclusion Ovary metastases from breast cancer are generally seen in the younger premenopausat patients with extraovarian metastases. The tumor sizes are generally small and are incidental found at therapeutic oophorectomy. An immunohistochemical panel consisting of GCDFP-15, mammaglobin, WT1 and CA125 is effective in distinguishing most of breast from ovarian cancers and is useful to find the small and tiny ovary metastases. Small bilateral ovarian enlargements and minor serum elevation of CA125 titers in patients with initial stage Ⅳ breast cancer, suffering from multiple metastatic disease, are likely to illustrate MOC.
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