Expression And Clinical Significance Of HIF1a And P53in Triple Negative Breast Cancer

Objective:Triple negative breast cancer(TNBC) is defined by the lack of protein of estrogen receptor(ER)、progesterone receptor(PR) and the absence of human epidermal growth factor2receptor(HER-2). TNBC is a subtype of breast cancer, with poor prognosis and no effective targeted therapy, as defined by low five-year survival and high recurrence rates and visceral metastasis, including brain metastasis. There is a clustering of TNBC cases in premenopausal women. So it is important to explore a new therapy to improve the prognosis of TNBC. In order to explore the role of the HIF1a and P53proteins in the development of TNBC and the relationship between the two proteins, we try to clarify the possible pathogenesis and prognostic factors of TNBC, in particular for the future, to investigate some novel targeted agents that may be beneficial for patients with TNBC.Methods:1. Clinical date45cases of TNBC specimens were collected, from January to December of2005year in Breast Cancer Department of Tianjin Cancer Hospital,30cases of NTNBC as a control group. All patients have no treatment before operation, diagnosed as non special type of IDC. The median age was51.2years(24-75years).2. Methods and Results The expression of HIF1a and P53proteins were stained with S-P method of IHC for all the patients. HIF1a protein to the cytoplasm or the nucleus was stained brown as a positive expression; P53protein to the nucleus stained yellow as a positive expression.3. Statistical analysis Comprehensive data analysis of clinical data, application SPSS17.0software data χ2test or Fisher probabilities and Spearman rank correlation testing method of the research were analyzed statistically. Test for P<0.05statistically significant.Results:1. Clinical epidemiology All the patients were female, age distribution of24-75years old, median age51.2years old.2. Immunohistochemical staining results 2.1The expression of HIF1a protein in TNBC Most HIF1a protein distributes in the cytoplasm; a small amount of the distribution in the nucles. HIF1a protein express positively in7cases of30patients with NTNBC, others express negatively; in TNBC group,25cases express positively, others express negatively. The difference of expression of HIF1a protein between the two groups was significant(χ2=7.640> P=0.006).2.2The relationship between expression of HIF1a protein and the pathological features of TNBC The expression of HIF1a protein have no significant difference between the factors such as age, menopausal status, family history, tumor size, recurrence and metastasis situation, the survival of the state(P>0.05). However, the differences of expression of HIFla protein between the factors such as histological grade, axillary lymph node metastasis were statistically significant(P<0.05).2.3The expression of P53protein in TNBC Most P53protein distributes in the nucles. P53protein express positively in10cases of30patients with NTNBC, others express negatively; in TNBC group,28cases express positively, others express negatively. The difference of expression of P53protein between the two groups was significant(χ2=6.010, P=0.014).2.4The relationship between expression of P53protein and the pathological features of TNBC The expression of P53protein have no significant difference between the factors such as age, menopausal status, family history, tumor size, recurrence and metastasis situation, the survival of the state(P>0.05). However, the differences of expression of P53protein between the factors such as histological grade,axillary lymph node metastasis were statistically significant(P<0.05).3. The correlation analysis between HIF1a and P53proteins Correlation analysis showed that HIFla protein and P53protein expression was positively correlated, the correlation coefficient r=0.318, p=0.033.Conclusions:1. Compared with NTNBC group, high positively expression of HIF1a and P53proteins in TNBC group may be the poor prognosis of patients with TNBC.2. The correlations between expression of HIF1a and P53proteins and the pathological features of TNBC such as histological grade, axillary lymph node metastasis have been made clearly. This implies that the two proteins could act as prognostic markers to judge the prognosis of TNBC.3. The expression of HIFla and P53proteins in TNBC was significantly positively correlated, suggesting that there may be positive feedback regulation mechanism between the HIF1a and P53proteins in the development of TNBC. In the future, the two proteins may become new targeting agents, this might represent further promising therapeutic options for patients with TNBC, but still need to be evaluated in appropriate clinical trials.