The Study Of The Relationship Between ER,PR,C-erB-2and Lung Adenocacinoma

Background:The incidence of lung cancer is highest in all kind of tumors, The treatment of lung cancer including surgery, chemotherapy, radiation therapy, targeted therapy, biological therapy and Chinese medicine. Endocrine therapy play an important position in the treatment of tumors, especially in breast and prostate cancer. In1982, American Pathologists Chaudhuri first reported estrogen and progesterone receptors exist in lung cancer. Later,more scholars confirmed that estrogen receptor and progesterone receptor exsit in lung cancer tissue through immunohistochemistry, Western blotting and RT-PCR methods. Mollerup et al found that ER-positive expression in NSCLC tissues was significantly higher than squamous cell carcinoma and small cell lung cancer. But the expression rate of estrogen receptor (ER), progesterone receptor (PR) in lung cancer still have obvious difference. There are many researchs about the relationgship between ER and PR expression and lung cancer prognosis, but get no definitive conclusions. So far, the relationship between ER,PR and lung cancer and its relationgship with prognosis is not clear yet, many views remains to be further explored.In lung cancer, bone is the common sites of metastases, bone-related events affect the quality of life and survival time of patients with lung cancer seriously, the median survival time after bone metastases in lung cancer is6-10months,1 year survival was40%. The mechanism of bone metastasis has not been determined. It is important and urgent to find the mechanism of lung cancer bone metastasis. As we know, breast, prostate and lung cancer is easy transfer to bone, breast cancer and prostate cancer has proved to be endocrine-related tumors, endocrine therapy is effective whether for primary lesions or bone metastases. The current studies have found that bone metastasis of breast cancer have relationship with estrogen receptor expression, The incidence of bone metastases is high if the rate of estrogen receptor expression is high. The highest incidence of bone metastases in various pathological types of lung cancer is lung adenocarcinoma. Onoe found that ERmRNA expression is high in the bone marrow in the femoral metaphysis and lumbar cancellous bone than the femoral shaft bone density mass. We can be seen that the type of high ER expression and the type of prone to bone metastases both are lung adenocarcinoma, The sites highly expressed of estrogen receptor corresponding to the sites easy to bone metastases. We thought whether bone metastases of lung adenocarcinoma have relationship with the expression of ER? there is no corresponding research in domestic and abroad research. PR is the product of estrogen-regulated gene, the activity and function sign of ER, C-erB-2have relationship with ER,and prognosis of lung cancer, thus PR and C-erB-2also included in the observations.Objective:To determine ER and PR, C-erB-2expression in lung adenocarcinoma patients's tumor tissues. Compared whether there are differences in ER,PR and C-erB-2expression in different subgroups. Further to explore whether there have relevance between these receptors expression in lung adenocarcinoma and bone metastasis, and analysis the ER and PR, C-erB-2expression in lung adenocarcinoma patient's survival and time of bone metastasis with multi-factor correlation analysis method. Early detect of lung adenocarcinoma patients prone to high risk of bone metastases in clinical work and provide better way to treat lung cancer ment.Methods:1.Detect ER and PR, C-erB-2expression levels in96tumor tissue specimens of lung adenocarcinoma patients by immunohistochemical methods, detected C-erB-2expression by fluorescence in situ hybridization (FISH) method if the C-erB-2is positive by IHC. Observe whether there have differences in ER, PR, C-erB-2expression in different gender, T stage, N stage and TNM stage group or not.2. Analysis whether the ER and PR, C-erB-2expression have correlation in different stage, degree of differentiation, bone metastases and overall survival time.3.Observe the relationship betwwen the ER and PR, C-erB-2expression.4.Observe whether the expression of ER and PR, C-erB-2in lung adenocarcinoma patients have difference betwwen bone metastasis group and non-bone metastasis,.Results:1.ER, PR, C-erB-2express in lung adenocarcinoma tissue. The positive expression rate of ER and PR in lung adenocarcinoma were23.9%,21.8%, the positive rate of C-erB-2were11.4%detected by immunohistochemistry method,6.3%positive by FISH method.2. There have no statistically significant difference in ER, PR and C-erB-2expression of lung adenocarcinoma between different gender, T stage, N stage and TNM stage group (P>0.05). The C-erB-2expression in different gender, T stage, N stage and TNM stage group have no significant difference by FISH detection method (P>0.05). If ER and C-erB-2is positive,the differentiation of lung adenocarcinoma was poor, ER (χ2=4.617P=0.032), C-erB-2IHC (χ2=4.210P=0.040), C-erB-2FISH (χ2=5.531P=0.019). There have no influence on C-erB-2expression between subgroups whether by immunohistochemistry or FISH. If ER and C-erB-2were positive, the adenocarcinoma were usually poorly differentiated or moderately differentiated.3. There have statistically significant differences in time to bone metastases and the average survival time between ER and C-erB-2positive and negative group (P<0.05). No statistical significance differences in the time to bone metastases and the average survival time between different gender group (P>0.05). There have statistical significance difference in the time to bone metastases and overall survival between different differentiation group (P<0.05). There have statistical significance difference in the time to bone metastases and overall survival between different T stage and N stage group (P<0.05), The lower T, N stage were, the longer the time to bone metastasis and overall survival time were. There have statistically significant differences in time to bone metastases and the average survival period between PR positive and negative group (P>0.05).4. The ER, PR and C-erB-2expression have no statistically significant differences between bone metastases and no bone metastases group (P respectively0.34,0.60,0.26), The C-erB-2expression detected by FISH have no statistical significance between bone metastases and no bone metastases group (P=0.65).but once bone metastases group ER, PR and C-erB-2expression, the level was higher, mostly++or+++, while the expression of these receptor in no bone metastasis group mostly+.the result have no statistically significant differences due to shortage number of cases.Conclusion:1. ER, PR, C-erB-2express in the primary lesion of lung adenocarcinoma.2.The expression level of C-erB-2detected by FISH method is lower than the immunohistochemical method, but there have no differences in expression between different subgroups.3.ER and C-erB-2are poor prognostic factors, the positive expression of ER and C-erB-2in lung adenocarcinoma patients indicate the time to bone metastases and the overall survival time shorter.4. ER, PR and C-erB-2expression in tumor tissue of lung adenocarcinoma have no relationship with bone metastasis or not. C-erB-2expression detected by FISH have no relationship with bone metastases.