Clinical Significance Of The Expression Of ER, C-erbB-2, And Nm23 In Breast Cancer

Breast cancer is one of the commonest malignant tumors in women. There were 1,200,000 women diagnosed of breast cancer and nearly 500,000 died of it each year.Also,there is an obvious increasing trend about 0.2%-8% in morbility in our country this century. Particularly in some big cities, the number of the dead caused by breast cancer has occupied the first of the feminine malignant tumor. Metastasis and recurrence of breast cancer are the common reason of death.So the key to reduce breast cancer mortality is to seek factors correlated with metastasis and recurrence,and take corresponding treatment.With the quick advancement of oncomolecularbiology, we realize that tumorigenesis progression of malignant tumor is a complex process involving polygene regulation, including activation of proto-oncogene, abnormalities of suppressor gene, metalloproteinases expression disorders with their inhibitors and a series of molecular disorders incident. So breast cancer prognosis indicators also become more diversified.Among the total, c-erbB-2, nm23 and ER are particularly important on the incidence, development, treatment options and prognosis of breast cancer.A large number of studies suggest that ER positive breast cancer is prevalent in high differentiation,good flexibility, little tissue necrosis,low lymphatic invasion,and long disease-free survival as well.However,C-erb-2 is closely associated with poor prognosis in breast cancer. Patient with C-erbB-2 positive is not only easy to transfer by blood,but also prone to lymphatic metastasis.People who is C-erbB-2 positive expression also significantly correlates with lower five year survival rate, no recurrence survival and overall survival rate compered with negative ones.Nm23 is called tumor metastasissuppressor gene. It can inhibit metastasis to axillary lymph node and distant place in breast cancer. Positive one is accompaniment with less axillary lymph nodes and distant metastases, higher five year survival rates.In order to further clarify the relevance and clinical characteristic of them,we analyzed 62 patients from August 1998 to January 2002 retrospectively, studying the relationship between each one with clinical characters which contain age, tumor size, pathology type, menstrual status, TNM stage, axillary lymph node metastasis, distant metastasis , live time and the relevance of themselves.We took 62 cases of breast cancer patients aged 24-80 years with an average age of 49.0 years and duration of 5-67 months. Their clinical stage was I stage(16),II stage(27),III stage(14),IV stage(5) according to UICC clinical stage standand.Their pathology tipies were invasive ductal carcinoma(36), invasive lobular carcinoma(7), ductal carcinoma(4), simple cancer (5), medullary carcinoma(7), mucinous carcinoma(3) according to the WHO histologic type . 51 of the patients were followed up for five years ,and five-year survival rate was 62.7%. All statistics were analyzed by SPSS 10.0 for window. Single factor was used x2 test to analyze prognosis factors in breast cancer. Kaplan-Meier method and Cox proportional hazard model were used to analyze the relationship of their expression with prognosis,with P<0.05 as notable difference in the judging criteria.The results showed that patients with ER positive were 27 cases, with the positive rate of 43.55% (27/62); 24 cases were C-erbB-2 positive expression, with the positive rate of 38.71% (24/60), 36 cases of nm23 positive expression accounted 58.06% (36/62)of all. The expression of nm23 was negativelyassociated with C-erbB-2 with correlation coefficient -0.533(P<0.01),and positively with ER, the correlation coefficient is -0.297(P<0.05),while the expression of C-erbB-2 was negatively associated with ER,the correlation coefficient is 0.285(P<0.05). ER positive rate of patients with TNM stage I, II, III, IV was 68.75%,37.03%,35.71%,20.00% (P<0.05)respectively. ER positive rate of patients whose survival time were more than five years was 56.25%,which is higher than the rate of 21.05%(P <0.05)which belong to whose survival time less than five years. C-erbB-2 positive rate of 24-35, 36-55, 56-80 years of age group was 72.73%, 34.15% and 20.00% (P<0.05) respectively. Among patients whose tumor diameter longer than 5.0 cm, 2.0 to 5.0cm and shorter than 2.0 cm groups,C-erbB-2 positive rate was 24.24%,52.17% and 66.67% (P <0.05) respectively. In patients with TNM stage I, II, III and IV, C-erbB-2-positive rate was respectively 12.50%,40.74%,57.14% and 60.00% (P<0.05). C-erbB-2 positive rate of patients with premenopause, axillary lymph node-positive, distant metastasis, survival time less than five years respectively was 53.13%,52.94%,50.00% and 57.89%,which was significantly higher than that of patients with post-menopause,axillary node-negative, no distant metastasis, survival more than five years:23.33%,21.43%,25.00% and 28.13% (P<0.05) respectively.Nm23 positive rate of 36-55, 56-80 age group was 69.69%, 52.17%,16.67%(P<0.05) respectively. Positive rate of TNM classification I was 87.5%, higher than that of stage II, III and IV:62.96%,28.57% and 20.00% (P<0.05). Nm23 positive rate of patients with axillary node-negative, no distant metastasis, survival more than five years were 75.00%, 85.71%,75.00%, which were significantly higher than that of patients with axillary lymph nodes,distant metastasis,survival time lessthan five years:44.12%,35.29%,42.11%(P<0.05). Kaplan-Meier method showed better overall survival time in patients with nm23 or ER positive expression than those without (P<0.05),and C-erbB-2 negative expression exhibited a significantly better prognosis than C-erbB-2 positive expression (P<0.05).In multivariate Cox regression analysis, the expression of C-erbB-2, and TNM stage were two important prognostic factors of breast carcinoma. The hazard ratios of C-erbB-2 expression and TNM stage was 4.918(P<0.01) and 4.452 respectively (P<0.05).To sum up, The expression of nm23 was negatively associated with C-erbB-2,and positively with ER,while the expression of C-erbB-2 was negatively associated with ER. Univariate analysis showed that ER positive patients were usually corresponding with early TNM stage,high survival advantage; C-erbB-2 positive ones were young,premenopause, with large tumor, late TNM stage, axillary lymph nodes and distant metastasis, short survival time; nm23 positive ones were usually corresponding with small tumor, early TNM stage, no axillary lymph nodes and distant metastases, long survival time. Multivariate analysis showed that C-erbB-2 and TNM stage were two independent adverse prognostic indicators in breast cancer.