Expression And Clinical Significance Of PTEN,HIF1α And VEGF In Breast Carcinoma

Breast cancer is one of the most common malignant tumor that hurts female health. Incidence of the disease has showed sharply asending trend in recent years.The age of onset goes to younger. Epidemic investigation has showed that breast cancer incidence rate aged 25 to 35 increases greatly in recent ten years and the average increasing rate can reach as high as 10.7%. The second disease peak is between 55 to 65 years old. Breast cancer has become the first or second female malignant tumor in some large or middle cities which is one of the main reasons of woman death. With the rapid development of molecular biology research in twentith century, gene theory of tumor development has been widely valued by scientists. Research results have shown that tumor developement is the result of multi-genes involving and influence of one another on many stages. Gene mutation can produce oncogene which lead to cell malignant development. The differentiation protein produced and coded by these oncogenes make cells grow and differentiate without ending which is the malignant character of tumor. Presently there are plenty of research of breast cancer genes and their influence factors which has become the focus of recent breast cancer research.. Now little is known about the relationship between the expression of PTEN , HIF1 α and VEGF proteins and tumorigenesis,differentiation,biological behavior and outcome of breast cancer.Inorder to analyze the relationship between the clinicopathological features and the expression of PTEl^ HDF1 a and VEGF proteins,we detected the expression of PTEN, HIF1 a and VEGF proteins by immunohistochemical method.This research discuss the probable disease mechnism and influence factors of prognosis of breast cancer from the epidemic and pathology angle, which provide lab evidence for directing clinic therapy,aidnosising diagnosis and judging prognosis of breast cancer. Materials and Methods 1 .PatientsIn this study,the samples were chosen from 44 cases of breast carcinoma who received radical resection at the Department of General Surgery, Zhujiang hospital of the First Military Medical University, from 2003-6 to 2004-12.They had been diagnosised correctly by common pathological examination.None of the patients had received radiotherapy,chemotherapy and other treatment before operation. The full clinical data had been collected. The mean age was 49.2 years (range from 26 -70) . 2.Method and Evaluation of ImmunostainingThe expression of PTEN\ HIF1 a and VEGF proteins was detected by immunohistochemical method. Clearly brown staining restricted to cytoplasm was considered as positive expression of PTEN protein. Clearly brown staining restricted to cytoplasm or nucleus was considered as positive expression of HIF1 a protein. Clearly brown staining restricted to cytoplasm was considered as positive expression of VEGF protein. 3. Statistical AnalysisSPSS 10.0 software was employed to analyze all data. Statistical evaluation was performed using Chi-Square test, Spearman's test. P<0.05 was considered as statistical significance. Results1.Clinical epidemiology:In 44 cases, all of cases is female.The age range is 26 yearsto 70 years.The medium age is 49.2 years.2.Results of immunohistochemistry staining:2.1. The expression of HIF1 a protein in the breast cancer: HDF1 a protein was maily restricted to cytoplasm ,and less was restricted to nucleus.In this study,there were 10 negative samples in the 10 cases of benign breast disease in Control.While in the 44 cases of breast cancer,there were 25posotive expression and 19 negative ones.The expression could be test in cytoplasm.Being compared with the control,the expression of HIF1 a protein in the cases of breast cancer was significantly different(X2= 10.580, P = 0.001).2.2. The relation between the expression of HIF1 a protein and the clinic pathologic character of breast cancenno differences were discovered in the expression of HIF1 a protein when the ages,the size of turner were considered( P >0 05).But,on the other hand,there were difference when the histological grade, axillary lymph node status, clinic TNM stage and the state of estrogen receptor were considered(P<0.05).2.3. The expression of PTNE protain in breast cancer: PTNE protain was maily restricted to cytoplasm.In this study,there were all positive expressions in the 10 cases of benign breast disease.While in the 44 cases of breast cancer,there were 23 posotive expression and 21 negative ones. Being compared with the control,the expression of PTNE protain in the cases of breast cancer was significantly different(Z2= 7.810, P = 0.001).2.4. The relation between the expression of PTNE protein and the clinic pathologic character of breast cancer: no differences were discovered in the expression of PTNE protein when the ages,the size of turner , histological grade and clinic TNM stage were considered(p>0 05).However,the high expression of proteinwas related with axillary lymph node status, the state of estrogen receptor were considered(P<0.05).2.5. The expression of VEGF protein in breast cancer: The positive expression of VEGF protein was maily restricted to cytoplasm.In this study,there were all negative expressions in the 10 cases of benign breast disease.While in the 44 cases of breast cancer.there were 33 posotive expression and 11 negative ones, and this was significantly different compared with the control (X2= 7.810, P = 0.001).2.6. The relation between the expression of VEGF protein and the clinic pathologic character of breast cancer: No differences were discovered in the expression of VEGF protein when the ages,the size of turner and the state of estrogen receptor were considered( P >0 05).But,on the other hand,the high expression of VEGF protein were related with the histological grade, axillary lymph node status, clinic TNM stage were considered(P<0.05).3.The correlation in the expression of HIF1 a ,PTEN andVEG: In the result of analysis by Spearman Test, the expression of HIF1 a shows significantly positive correlation with that of VEGF(rs= 0.344, p= 0.022),while ,the the expression of HIF-1 a shows significantly negative correlation with that of PTEN(rs= - 0.374, p = 0.012).The correlation between the expression of PTEN and VEGF was negative but not significently(r=-0.236,P= 0.122). The result showed that those three proteins were correlated with each other in human breast cancer.The absence of PTEN enhanced the transcription of VEGF, VEGF may be the primary downstream genes of HIF-1 in breast cancer.. Conclusion:According to this lab data, we can speculate that HIFla,PTEN and VEGF correlate significantly and play a key role in breast cancer occuring,developement, metastasis and prognosis. Advanced research has shown that PTEN, HIFla andVEGF proteins help somewhat in indicating breast cancer mechnism. Their expressions are related to part of breast cancer clinic pathologic characters and worthy in clinic judge of breast cancer prognosis and advanced therapy. In breast cancer tissues, HIFla expression is correlate significantly positive with VEGF experession and PTEN is correlate significantly negative with HIFla experession. The negative correlation between PTEN and VEGF expression shows PTEN may adjust negatively HIFla expression and depress VEGF expression through PI3K/AKT signal transfer passage.