Abstract: Objective:To detect the expressions of hypoxia inducible factor-1α (HIF-1α) and epithelialmesenchymal transformation (EMT)related factors Ecadherin and vimentin in tumor tissues and adjacent tissues of esophageal squamous cell carcinoma (ESCC), analyze the correlation of expressions in tumor tissues, and investigate the relationship between expressions and clinicopathological factors or prognosis.
Methods:The retrospective casecontrol study was conducted. The clinicopathological data of 116 patients with ESCC who were admitted to the Cancer Hospital of Tianjin Medical University between January 2006 and December 2009 were collected. The expressions of HIF-1α, Ecadherin and vimentin in tumor tissues and adjacent tissues of ESCC were detected by immunohistochemistry (IHC). Observation indicators: (1) the expressions of HIF-1α, Ecadherin and vimentin in tumor tissues and adjacent tissues; (2) the correlations among expressions of HIF-1α, Ecadherin and vimentin in tumor tissues; (3) the relationship between clinicopathological factors of patients with ESCC (gender, age, tumor location, tumor differentiation, tumor diameter, depth of tumor invasion, lymph node metastasis, TNM stage) and positive expressions of HIF-1α, Ecadherin and vimentin; (4) the relationship between prognosis and expressions of HIF-1α, Ecadherin and vimentin in tumor tissues. The followup using outpatient examination and telephone interview was performed to detect the survival up to December 2014. Comparison of count data was analyzed using the chisquare test. Correlation analysis was done using the Spearman rank correlation analysis. Survival rate was calculated using the KaplanMeier method and survival analysis was done using the Logrank test.
Results:(1) The expressions of HIF-1α, Ecadherin and vimentin in tumor tissues and adjacent tissues: the positive expressions of HIF-1α in tumor tissues and adjacent tissues were respectively 50.86%(59/116) and 22.22%(8/36), with a statistical difference (χ²=9.142, P<0.05). The positive expressions of Ecadherin in tumor tissues and adjacent tissues were respectively 25.00%(29/116) and 52.78%(19/36), with a statistical difference (χ²=9.811, P<0.05). The positive expressions of vimentin in tumor tissues and adjacent tissues were respectively 32.76%(38/116) and 11.11%(4/36), with a statistical difference (χ²=5.401, P<0.05). (2) The correlations among expressions of HIF-1α, Ecadherin and vimentin in tumor tissues: 7 patients had positive expressions of HIF-1α and Ecadherin, 35 had negative expressions of HIF-1α and Ecadherin, 52 had positive expression of HIF-1α and negative expression of Ecadherin and 22 had negative expression of HIF-1α and positive expression of Ecadherin. Twentyeight patients had positive expressions of HIF-1α and vimentin, 47 had negative expressions of HIF-1α and vimentin, 31 had positive expression of HIF-1α and negative expression of vimentin and 10 had negative expression of HIF-1α and positive expression of vimentin. Results of Spearman rank correlation analysis showed that there was a negative correlation between expression of HIF-1α and expression of Ecadherin in tumor tissues (r=-0.624, P<0.05) and a positive correlation between expression of HIF-1α and expression of vimentin in tumor tissues (r=0.319, P<0.05). (3) The relationship between clinicopathological factors of patients with ESCC and positive expressions of HIF-1α, Ecadherin and vimentin: number of patients with positive expressions of HIF-1α, Ecadherin and vimentin was 11, 14, 6 in stage T1-2 of depth of tumor invasion, 48, 15, 32 in stage T3-4 of depth of tumor invasion, showing significantly statistical differences in positive expressions of HIF-1α, Ecadherin and vimentin in tumor tissues of patients with different depth of tumor invasion (χ²=7.574, 6.014, 5.549, P<0.05). Number of patients with positive expressions of HIF-1α, Ecadherin and vimentin was 24, 23, 12 without lymph node metastasis and 35, 6, 26 with lymph node metastasis, showing significantly statistical differences in positive expressions of HIF-1α, Ecadherin and vimentin in tumor tissues of patients with or without lymph node metastasis (χ²=8.992, 9.739, 11.768, P<0.05). Number of patients with positive expressions of HIF-1α, Ecadherin and vimentin was 0, 3, 0 in stage Ⅰ of TNM stage and 27, 19, 15 in stage Ⅱ of TNM stage and 32, 7, 23 in stage Ⅲ of TNM stage, showing significantly statistical differences in positive expressions of HIF-1α, Ecadherin and vimentin in tumor tissues of patients with different TNM stage (χ²=17.215, 10.448, 13.018, P<0.05). (4) The relationship between prognosis and expressions of HIF-1α, Ecadherin and vimentin in tumor tissues: 116 patients were followed up for 18.0-96.0 months, with a median time of 62.3 months. The median survival time and 5year cumulative survival rate were 18.0 months and 27.5% in patients with positive expression of HIF-1α, 40.0 months and 43.6% in patients with negative expression of HIF-1α, with a significantly statistical difference (χ²=5.657, P<0.05). The median survival time and 5year cumulative survival rate were 24.0 months and 28.4% in patients with positive expression of Ecadherin, 33.0 months and 38.9% in patients with negative expression of Ecadherin, with no statistical difference (χ²=2.469, P>0.05). The median survival time and 5year cumulative survival rate were 31.0 months and 36.9% in patients with positive expression of vimentin, 22.0 months and 29.7% in patients with negative expression of vimentin, with no statistical difference (χ²=1.167, P>0.05).
Conclusions:The expressions of HIF-1α and vimentin in tumor tissues are increased, and expression of Ecadherin is reduced. A negative correlation between expression of HIF-1α and expression of Ecadherin and a positive correlation between expression of HIF-1α and expression of vimentin are detected, which may promote EMT of ESCC. The expressions of HIF-1α, Ecadherin and vimentin are correlated closely with depth of tumor invasion, lymph node metastasis and TNM stage. Patients with positive expressions of HIF-1α have the poor prognosis.