Expression Of HIF-1α, VEGF, CD105 And Their Relationship With Angiogenesis In Esophageal Squamous Cell Carcinoma

Background and objectsHypoxia is a basic characteristic of micro-enviroment of solid tumors. Angiogenesis and cellular adaptation to hypoxia represent critical step in tumorigenesis.The key factor regulating cellular O₂ homeostasis is hypoxia-inducible factor-1(HIF-1), HIF-1αis a subunit of HIF-1, is the only subunit of Oxygen regulation, which can decide the activity of HIF-1α. Its activity plays important roles in maintaining the energy metabolism of tumor cells, in the new angiogenesis and in promoting the rumor's multiplication, invasion and metastasis.Our country is a region of high incidence of esophageal carcinoma. ESCC occupies 90% of all esophageal carcinomas. Carcinogenesis,development,infiltration and metabasis of ESCC all depend on the vascular formation. Untill now, Vascular endothelial growth factor(VEGF) is the most prominent angiogenic growth factor, whose expression is regulated by many factors, of which hypoxia is the strongest inducer of VEGF expression. HIF-1αplays a key role in the hypoxic induced VEGF gene expression upregulation. CD105 is a specific and sensitive marker for tumor angiogenesis. It is an antigen of endothelial cellular membrane which is related with hyperplasy. It has intensive expression in endodermis of new vessels relating with tumors. And CD105 is a fairly precise index in measuring endodermis vegetative state. The specificity is high if CD105 is chose to brand microvessel density (MVD).Material and methodsImmunohistochemical Method (s-p) was applied to detect the differential expressions of HIF-1α, VEGF and CD105 in 56 ESCC specimens and 20 normal esophageal mucosa. Then we counted MVD, As for the statistical processing, We used Spss 11.0 statistics software.Results1. The positive expression of HIF-1αwas lied in cell nucleus, Results of IHC showed that the expression of HIF-1αwas correlated with clinical stage and lymph node metastasis. It was not expressed in 20 normal tissues, The positive rate of HIF-1αin the advanced stage (63.41%,26/41) was higher than that of in the earlier stage (33.33%, 5/15) (P < 0.05); HIF-1αwith lymph node metastasis (66.67%,24/36) was higher than that without lymph node metastasis (35.00% , 7/20) (P < 0.05). The expression of HIF-1αwasn't correlated with age, sex, location, the depth of invasion and histological grade( P > 0.05).2. The positive expression of VEGF was lied in cell cytopllasm, Results of IHCshowed that the expression of VEGF was correlated with clinical stage, the depth of invasion and lymph node metastasis. It was poorly expressed in only 2 normal tissues, positive rate of VEGF in the advanced stage (63.41%,26/41) was higher than that of in the earlier stage (46.67%,7/15) (P < 0.05);VEGF with deeply infiltrating (78.79%,26/33) was higher than that with superficially infiltrating (47.62%,10/21) (P < 0.05); VEGF with lymph node metastasis (77.78%,28/36) was higher than that without lymph node metastasis (40.00%,8/20) (P < 0.05). The expression of VEGF wasn't correlated with age, sex, location and histological grade (P>0.05). 3. The results of the counted number of MVD in cancer tissues revealed: MVD in theadvanced stage (35.84±5.24) was significantly higher than that of in the earlier stage (26.24±4.43); MVD with lymph node metastasis (35.57±5.68) was significantly higher than that without lymph node metastasis (29.13±6.18); MVD with deeply infiltrating (36.79±4.48) was significantly higher than that with superficially infiltrating (27.40±5.22), all the difference had statiscal significance (P<0.01).4. There was a close correlation between the expression of HIF-1αand VEGF. The positive rates of VEGF in the HIF-1αpositive group 90.3% (28/31) was higher than that in the negative group 32.0% (8/25) (P < 0.01). There was a trend that the positive rates of VEGF were progressively increased with the increase of the extent of the expression of HIF-1α.5. There was a close correlation between the expression of HIF-1α, VEGF and MVDin ESCC. MVD was 36.18±5.89 in HIF-1α-positive group, which was much higher than 29.66±5.61 in HIF-1α-negative group (P<0.01); MVD was 36.65±4.76 in VEGF-positive group, which was much higher than 27.18±4.82 in VEGF-negative group(P<0.01); MVD increased with the increase of the extent of the expression of HIF-1αand VEGF.Conclusions1. The expression of HIF-1αand VEGF were much higher than the normal esophagus tissue, their expressed levels reflected infiltrating, metastasis, Indicating their potential prognosis value and the hopeful of becoming a new marker to the prognosis evaluation of ESCC.2. HIF-1αdidn't express in normal tissues,But it had a high expression in cancertissues.Which indicated that it may become a biological index that differentiating normal tissues and cancer tissues.3. MVD value had significant correlation with tage of the disease, the depth of invasion and lymph node metastasis, Indicating that MVD was a biological behaviours, Which assisted HIF-1αand VEGF to judge tumor malignancy and prognosis of ESCC.4. The consistency existed in the expressions of HIF-1αand VEGF in ESCC, Andthe MVD in the positive groups were much higher, their expression had consistency, Which verificating HIF-1αplayed an important role in the building of esophagus cancer's blood vessel by depending on the expression of VEGF. So it may be a new target for the inhibition of angiogenesis by restraining the expression of HIF-1α.