| Background and Objective Breast cancer is one of the most common malignancy of women, its morbidity is increasing year by year. Although the clinical and pathological parameters such as age, tumor, size, tumor location, histological grade, axillary lymph node status, expression of ER,PR,Her-2 and et al, played an important role in the treatment and the evaluation of prognosis. As breast cancer is a kind of highly heterogeneity tumor, even if the clinical stage of patients is basically consistent to the pathological grades, there are differences in the development history, biological behavior and the treatment response, which suggests that there maybe other factors exist and affect the developing, treatment and prognosis of breast cancer. Therefore, it has great significance to do some research on the mechanism of carcinogenesis, development and metastasis, to find out valuable marker and therapeutic targets, and to seek for effective means of prediction and prevention of breast cancer. In the present study, we selected AhR and ARNT which are key molecules in this process of breast cancer.Both AhR and ARNT belong to the bHLH-PAS transcription factor superfamily. It is reported that they are associated with tumorigenesis, for example, the expression of them in different tumor tissues. Besides these, the relationship between the expression of them in different breast status and clinical pathological data has not been reported yet. As we know, cancerous is a a multi step and multi period procedure. Some scholars considered that the initiation and progression of breast cancer experienced a process:benign proliferative lesionsâ†'precancerous lesionsâ†'carcinoma in situâ†'invasive carcinoma. The experiment will use the theory to study the expression of AhR/ARNT in different breast tissues, explore and analyze the relationship between the expression of them and clinical pathological status of breast cancer.Methods Using the immunohistochemical staining method to detect the expression of the AhR and ARNT in various kinds of breast disease tissues:lobular hyperplasi, cystic hyperplasia, carcinoma in situ and invasive breast carcinoma. And analyze the relationship of these two markers in patients with clinical and pathological parameters.Results 1-, The positive staining of AhR in cytoplasm and nucleus was seen, maily in nucleus; ARNT staining was in nucleus; The staining of both in tumor cell proliferation area and fission cells was significantly enhanced.2,The positive expression rate of the AhR in breast lesion tissues: breast lobular hyperplasia:30.00%(6/20); breast cystic hyperplasia: 31.25%(5/16); breast carcinoma in situ:50.00%(4/8); invasive breast carcinoma:72.50%(29/40), which contains two histopathological types:invasive ductal carcinoma and invasive lobular carcinoma, and the rate of them respectively were 70.83%(17/24),75.00%(12/16). The total positive rate of breast cancer group was 68.75%(33/48) and the rate of non-cancer group was 30.55%(11/36); The rate of group without lymph node metastasis was 61.54%(16/26) and the rate of lymph node metastasis group was 77.27%(17/22).The positive expression rate of the AhR nuclear translocation:breast lobular hyperplasia:25.00%(5/20); breast cystic hyperplasia: 31.25%(5/16); breast carcinoma in situ:37.50%(3/8); invasive breast carcinoma:67.50%(27/40), which contains two histopathological types: invasive ductal carcinoma and invasive lobular carcinoma, and the rate of them were 62.50%(15/24),75.00%(12/16). The total positive rate of breast cancer group was 62.50%(30/48) and the rate of non-cancer group was 30.55%(11/36); The rate of group without lymph node metastasis was 57.69%(15/26) and the rate of group with lymph node metastasis was 68.18%(15/22).From breast lobular hyperplasia and breast cystic hyperplasia to carcinoma in situ cacinoma in situ, especially to invasive carcinoma, the positive expression rate of AhR and AhR nuclear translocation showed a trend of gradually increasing (p< 0.05), but unrelated with the histopathological types and the presence of lymph node metastasis(p> 0.05).3,The positive expression rate of the ARNT in breast lesion tissues: breast lobular hyperplasia:30.00%(6/20); breast cystic hyperplasia: 50.00%(8/16); breast carcinoma in situ:75.00%(6/8); invasive breast carcinoma:80.00%(32/40), which contains two histopathological types: invasive ductal carcinoma and invasive lobular carcinoma, and the rate of which were 79.17%(19/24),81.25%(13/16). The total positive rate of breast cancer group was 79.17%(38/48) and the rate of non-cancer group was 41.67%(15/36); The rate of group without lymph node metastasis was 76.92%(20/26) and the rate of lymph node metastasis group was 81.82%(18/22).From breast lobular hyperplasia and breast cystic hyperplasia to carcinoma in situ, especially to invasive carcinoma, the positive expression rate of ARNT showed a trend of gradually increasing (p< 0.05), but unrelated with the histopathological types and the presence of lymph node metastasis(p>0.05).4,Spearman correlation analysis showed that the expression of AhR and ARNT in nuclear was positively correlated in various stages of breast tissues(rs=0.355,p<0.05).5,The expression of AhR and ARNT were unrelated with age, menstrual status, tumor location and size, clinical stage, ER and Her-2 expression of patients. There was no correlation between the expression of ARNT and PR(p>0.05), but the expression of AhR and PR was positively correlated(rs=0.342,p< 0.05). In patients with the positive expression of PR, the positive expression of AhR was 82.14% (23/28).Stratified analysis showed that in ER-positive and Her-2 positive patients, AhR and PR expression was significantly and positively associated, P values were 0.000,0.040, and r values were 0.728,0.598.Conclusion 1,The expression of AhR and ARNT in the multi-stage breast lesion shows a trend of gradually increasing. Both of them have a high rate of expression in breast cancerous tissues. This suggests that AhR and ARNT might play a significant role in the initiation and progression of breast cancer.2,The expression of AhR is positively correlated with the expression of PR. We speculates that AhR may acts as a new marker which can predict the sensitivity of endocrine therapy and the clinical prognosis. |
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