Expression And Biological Relationships Of HIF-1α, P53, VEGF In The Carcinoma Of Esophagus

Objective: Esophageal carcinoma is one of the highincidence carcinomas in malignant digestive tumors in ourcountry. Patients with esophageal carcinoma often died frommetastasis of esophageal carcinoma. It has been known thatcombined biological effects of multiple genes and multiplefactors were involved in the carcinogenesis of esophagealepithelium and metastasis of esophageal carcinoma. Toinvestigate the expression of Hypoxia inducible Factor-1α(HIF-1α), P53, Vascular endothelial growth factor (VEGF) inesophageal carcinoma and the relationships to biologicalbehavior of the cancer. This experiment is to investigaterelationships between expression of HIF-1αand VEGF and theircorrelation to invasion and metastasis in esophageal cancer; toinvestigate relationships between expression of HIF-1αand P53and their correlation to invasion and metastasis in esophagealcancer; to investigate the effect of HIF-1αon angiogenesis. Theresults may be helpful in prognostication of esophageal cancer.Methods1. The expression of HIF-1αprotein, P53 protein and VEGFprotein was examined by s-p immunohistochemical stain (IHC)in 51 esophageal carcinoma specimens and 26 para-tumorous and23 incisal margin normal tissues.2. The expression of HIF-1αmRNA in 51 esophageal carcinomaspecimens, 26 para-tumorous and 23 incisal margin normaltissues was examined by In situ hybridization (ISH). Results1. Expression of HIF-1αin various lesions esophageal epithelialThere was a significant difference in 41 esophagealcarcinoma specimens (80.4%) and 18 para-tumorous esophagealtissues (69.2%) and 3 incisal margin normal tissues (13.3%)which were quantitatively examined by ISH, and expression ofHIF-1αin esophageal carcinoma was significantly higher than inpara-tumorous esophageal tissues and incisal margin normaltissues. It showed that esophageal carcinoma cell had a strongcapability to secret HIF-1α.There was a significant difference in 39 esophagealcarcinoma specimens (76.5%), 16 para-tumorous esophagealtissues (61.5%) and 2 incisal margin normal tissues (8.6%) whichwere quantitatively examined by IHC, and expression of HIF-1αin esophageal carcinoma was significantly higher than inpara-tumorous esophageal tissues and incisal margin normaltissues. It showed that esophageal carcinoma cell had a strongcapability to secret HIF-1α.Results of ISH and IHC showed that the expression ofHIF-1αwasn't correlated with age, sex and tumor differentiation,but the high expression of HIF-1αin cancer tissues wassignificantly related with the depth of invasion and lymph nodemetastasis.2. Expression of VEGF in various lesions of esophagealepithelialThere was a significant difference in 35 esophagealcarcinoma specimens (68.2%), 10 para-tumorous esophagealtissues (38.5%) and 1 incisal margin normal tissues (4.3%) werequalitatively examined by IHC, and expression of VEGF inesophageal carcinoma was significantly higher than inpara-tumorous esophageal tissues and incisal margin normaltissues. It showed that esophageal had a strong capability tosecret VEGF.Results of IHC showed that expression of VEGF wasn'tcorrelated with age and sex, but the high expression of VEGF incancer tissues were significantly related with the depth ofinvasion, lymph node metastasis. And there was a significantdifference in well differatiation esophageal carcinomas (36.4%),moderate differatiation esophageal carcinomas (61.1%) and poordifferatiation esophageal carcinomas (90.9%).3. Expression of P53 in various lesions of esophageal epithelialThe experiments showed that there was no significantlydifference in 30 esophageal carcinoma specimens (58.8%) and 15para-tumorous esophageal tissues (57.7%), but the expression ofP53 in esophageal carcinoma and para-tumourous esophagealtissues was significantly higher than in incisal margin normaltissues (0%). Expression of P53 wasn't correlated with age, sexand lymph node metastasis, but the high expression of P53 incancer tissues was significantly related with the depth ofinfiltration. And there was a significant difference in welldifferatiation esophageal carcinomas (27.3%), moderatedifferatiation esophageal carcinomas (61.1%) and poordifferatiation esophageal carcinomas (72.7%).4. The relationship between HIF-1αand VEGF There was a positive correlation between expression ofHIF-1αand expression of VEGF (χ2=4,P<0.05).5. The relationship between HIF-1αand P53 There was a positive correlation between expression ofHIF-1αand expression of P53 (χ2= 4.263,P<0.05).6. The relationship between VEGF and P53There was no positive correlation between expression ofVEGF and expression of P53 (χ2=1.471,P>0.05).cell carcinoma was significantly higher than that of VEGF innormal esophageal tissues, which indicated that VEGF couldinvolve in tumorigenesis progressin. The expression of VEGF inesophageal squamous cell carcinoma with lymph node metastasiswas significantly higher than that of VEGF in esophagealsquamous cell carcinoma without lymph node metastasis. Itindicated that the high expression of VEGF was related withinvasion and metastasis of esophageal squamous cell carcinoma.3. The expression of P53 protein in esophageal squamous cellcarcinoma was significantly higher than that of P53 in normalesophageal tissues, it indicated that P53 could involve intumorigenesis progression.4. There was a positive correlation between expression of HIF-1αand VEGF, as we known there was a positive relationshipbetween VEGF and angiogenesis, so the results indicated thatHIF-1αmight be one of the important factors in angiogenesis ofesophageal squamous cell carcinoma.5. There was a positive correlation between HIF-1αand P53 inesophageal squamous cell carcinoma, as we known there was arelationship between mutant P53 and carcinomatous change,which showed that HIF-1αmight be one of factors to acceleratethe processes of carcinomatous change.6. There was no significant correlation between VEGF and P53in esophageal squamous cell carcinoma in this experiments,which wasn't corrected with some literatures, the reason may be...