Abstract: Objective:To detect the expressions of the second mitochondriaderived activator of caspase protein(Smac) and Survivin in tissues of highgrade intraepithelial neoplasia（HGIN）and esophageal squamous cell carcinoma (ESCC), and explore the influence of Smac and Survivin on occurrence and development of ESCC.
Methods:The retrospective casecontrol study was conducted. The clinicopathological data of 45 healthy controls with suspected esophagitis (control group), 41 patients with HGIN (HGIN group) and 57 patients with ESCC (ESCC group) who were admitted to the Qinghai University Affiliated Hospital between January 2012 and December 2014 were collected. Observation indicators included: (1) expressions of Smac and Survivin were detected by immunohistochemistry. (2) Expressions of mRNA of Smac and Survivin in tumor tissues and adjacent tissues were detected by realtime polymerase chain reaction (RTPCR). (3) Correlation between relative expressions of Smac and Survivin in tumor tissues and adjacent tissues. (4) Relationship between expressions of Smac and Survivin in tumor tissues and clinicopathological factors. Measurement data with normal distribution were represented as ±s. The comparisons among groups was evaluated with the oneway ANOVA. The comparison between tumor tissues and adjacent tissues were analyzed by the paired t test, and comparison of rates was done using the chisquare test and Fisher exact probability. The correlation between expressions of Smac and Survivin was done using the Pearson correlation analysis.
Results:(1) Expressions of Smac and Survivin were detected by immunohistochemistry. The positive expression rate of Smac of esophageal tissues in the control group, HGIN group and ESCC group were respectively 82.2%(37/45), 43.9%(18/41) and 40.4%(23/57), with a statistically significant difference among the 3 groups (χ²=20.408, P<0.05). There were statistically significant differences in the positive expression rate of Smac between control group and HGIN group or ESCC group (χ²=13.665, 18.202, P<0.05) and no statistically significant difference between HGIN group and ESCC group (χ²=0.124, P>0.05). The positive expression rate of Smac of adjacent tissues in the ESCC group was 84.2% (48/57), with a statistically significant difference between tumor tissues and adjacent tissues (χ²=20.530, P<0.05). The positive expression rate of Survivin of esophageal tissues in the control group, HGIN group and ESCC group were respectively 11.1%(5/45), 70.7%(29/41) and 68.4%(39/57), with a statistically significant difference among the 3 groups (χ²=41.963, P<0.05). There were statistically significant differences in the positive expression rate of Survivin between control group and HGIN group or ESCC group (χ²=31.901, 33.672, P<0.05) and no statistically significant difference between HGIN group and ESCC group (χ²=0.060, P>0.05). The positive expression rate of Survivin of adjacent tissues in the ESCC group was 15.8%(9/57), with a statistically significant difference between tumor tissues and adjacent tissues (χ²=32.386, P<0.05). (2) The relative expressions of mRNA of Smac and Survivin which were detected by RTPCR were 0.66±0.09 and 0.92±0.15 in tumor tissues, 1.02±0.17 and 0.47±0.13 in adjacent tissues, respectively, with statistically significant differences (t=-16.939, 15.190, P<0.05). (3) Correlation between relative expressions of Smac and Survivin in tumor tissues and adjacent tissues: there was no correlation in relative expressions of Smac and Survivin in tumor tissues (r=0.275, P>0.05) and in adjacent tissues (r=-0.197, P>0.05). There was a correlation in the relative expression of Smac between tumor tissues and adjacent tissues (r=0.527, P<0.05) and no correlation in the relative expression of Survivin between tumor tissues and adjacent tissues (r=0.035, P>0.05). (4) The relationship between the expressions of Smac and Survivin in tumor tissues and clinicopathologic factors: the positive expression of Smac in tumor tissues was 51.6% in men, 9.1% in women, 64.7% in tumor diameter<3 cm, 28.0% in tumor diameter≥3 cm, 60.0% in stage Ⅰ-Ⅱ of TNM stage and 22.7% in stage Ⅲ-Ⅳ of TNM stage, respectively, showing statistically significant differences in the positive expression of Smac in tumor tissues of patients with different gender, tumor diameter and TNM stage (χ²=6.093, 5.567, 6.041, P<0.05). The positive expression of Survivin in tumor tissues was 54.5% in high and moderatedifferentiated tumors, 100.0% in lowdifferentiated tumors, 75.0% in stageⅠ-Ⅱ and 100.0% in stage Ⅲ-Ⅳ, respectively, showing statistically significant differences in the positive expression of Survivin in tumor tissues of patients with different tumor differentiation and TNM stage (P<0.05).
Conclusions:The expression of Smac in the progression of esophageal epithelial cells towards to highgrade intraepithelial neoplastia and proliferatoin is inhibited, while expression of Survivin is activated. Smac and Survivin participate in the occurrence of ESCC and maybe play an role in determining the biological features of carcinoma tissues.