The Expression Of HIF-1α, VEGF And MVD And Their Relationship With The Biological Behavior In Breast Carcinoma

Hypoxia inducible factor, HIF-1 is a kind of mediate hypoxic adaptable transcription factor which lies in mammals and human cells. Research indicates that it widely lies in many kinds of human tumor cells, which is a key protein that directly reacts to the oxygen deficit. HIF-1 α is a subunit of HIF-1, is the only sub-unit of oxygen regulation, which can decide the activity of HIF-1. Its activity plays important roles in maintaining the energy metabolism of tumor cells, in the new angiogenesis and in promoting the tumor's multiplication, invasion and metastasis. It was also modulated and influenced by many other factors. The protein over-expression of HIF-1 α lies in many kinds of malignant tumors, which closely related to the poor prognosis. By far, there is no research on the relationship between the development and progression of the breast cancer and the HIF-1 α in China.Vascular endothelial growth factor (VEGF) is one of the main cell factors of the tumor which induced the new blood vessels. It is also the discovered best key factors which can stimulate the tumor angiogenesis. Its expression under the hypoxia environment modulated by HIF-1 α . HIF-1 plays a key role in the hypoxic induced VEGF gene expression upregulation. The develepment and metastasis of malignant tumor depents on its angiogenesis . VEGF's high expression in the breast tumor increases the tumor angiogenesis and promotes the multiplication, invasion and metastasis, which is an indicator of poor prognosis and closely related to the micro-vessel density, tumor differentiation and the metastasis of lymph node.Material and method :All the tissue samples are selected from the filed wax pice (2002-2003) in the department of pathalogy of the No.1 affiliated hospital to Zhengzhou university. Immunohistochemical Method (s-p) was applied to probe into relationship between HIF-1α and VEGF vascularization by studing HIF-1 α ,VEGF and CD34 of 68 breast cancer samples and their relationship with other clinial pathalogical factors such as metastasis, histological classification was also studied such .As for the statistical processing, Spss10.0 was used to do x2 analysis, t analysis and variance analysis. The relationship between HIF-1 α ,VEGF and MVD was analyzed by using spearman rank correlation. Results :The positive expressions of protein HIF-1 a and protein VEGF in 68 breast cancer cases are respectively 54.41% (37 / 68) and 61.67% ( 42 / 68). The consistency exists in the expressions of HIF-1 α and VEGF in breast cancer's tissue (p > 0.05). (2). The MVD values are 24.18 ±7.69 and 23.09 ± 7.66 in the HIF-1 α and VEGF's positive expression group in the tissue of breast cancer, which are apparently above those in HIF-1 α and VEGF's negative expression group 16.35 ± 5.46 and 16.61 ± 6.24 (p<0.01). (3). With the increase of HIF-1 α and VEGF's positive expression, MVD value distinctly increases .The MVD value is in its highest level when both HIF-1 α and VEGF show positive results (p<0.01), which is distinctly higher than other groups. Reversely, the MVD value is in its lowest level when VEGF and HIF-1 α show negative results. The expression of HIF-1 α and VEGF significantly correlated with the expression of MVD in breast cancer(p<0.05). (4). The positive expression of protein HIF-1 α in lymph node metastasis group is 65.11% (28 / 43), the positive expression in non-metastasis is 36.00% (9 /25). There is an apparent difference between the two groups (p <0.05). (5). The positive expressions of HIF-1 a in the classification of Ⅰ , Ⅱ, and Ⅲ in breast cancer histology are respectively 25.00% (4 / 16), 48.14% (13 /27), and 80.00% (20 / 25). There are clear differences among the three classifications (p<0.05). Its expression shows a gradually ascendingtrend with cancer 's degree of differentiation. (6). The positive expression of protein VEGF in lymph node metastasis group is 74.41% (32/ 43), and 40.00% (10/25) in non-metastasis group. There is a clear difference between the two groups (p<0.01). (7). The positive expressions of VEGF in the classification of Ⅰ , Ⅱ, and Ⅲ in breast cancer histology are respectively 43.75% (7 /16), 51.85% (14/27), and 84.00% (21 / 25). There are clear differences among the three classifications (p<0.05). With the worsening degree of the cancer, the positive expression increases. Conclusion:1. HIF-1 α in breast cancer's tissue exists overexpression. It probably participates in the evolvement and development of breast cancer.2. HIF-1 α plays an important role in the building of breast cancer's blood vessel by regulating the expression of VEGF.3. The consistency exists in the expressions of HIF-1 α and VEGF in breast cancer's tissue.4. The expression of HIF-1 α and VEGF significantly correlated with the expression of MVD in breast cancer.5. The overexpressions of HIF-1 α and VEGF and MVD have relation with the ill development of breast cancer. It can be an important index for forecasting breast cancer's invasion, metastasis and prognosis.