Expression Of GRP78, Caspase-4, NF-κB / P65 And Bcl-2 In Gastric Carcinoma And Precancerous Lesions

Objective:By detecting the expression of GRP78, Caspase-4, NF-κB/p65and Bcl-2in gastric carcinoma and precancerous lesion to analyze their relationships with clinical-pathologic and their expressed relationships in gastric carcinoma and precancerous lesion, thereby to investigate the role of endoplasmic reticulum stress response in the gastric carcinoma development.Methods:Immunohistochemistry was used to measure levels of the expressions of GRP78, Caspase-4, NF-icB/p65and Bcl-2in the gastric carcinoma and precancerous lesions. The gastric carcinoma and precancerous lesion tissue specimens were obtained from35cases of gastric carcinoma,30cases of high grade dysplasia,30cases of intestinal metaplasia and20cases of superficial gastritis tissues.Results:(1) The positive expression rates of GRP78in chronic superficial gastritis tissues, intestinal metaplasia, dysplasia and gastric carcinoma were15.0%,46.7%,80%and91.4%respectively. The positive expressions of GRP78in the teams of superficial gastritis and intestinal metaplasia had significant statistic difference (P=0.021), also in the teams of intestinal metaplasia and dysplasia (P=0.007), the other group was not statistically significant (P=0.332). The positive expressions of GRP78in the teams of well-differentiated and moderately and poor-differentiated were62.5%(5/8) and100.0%(27/27) respectively, the difference between the two terms had significant statistic difference (P=0.009). The positive expressions of GRP78in the teams of phase Ⅰ+Ⅱ and Ⅲ+Ⅳ were57.1%(4/7) and100.0%(28/28) respectively, the difference between the two terms had significant statistic difference (P=0.005). The positive expressions of GRP78in the teams of gastric carcinoma with lymphatic metastasis and without lymphatic metastasis were100.0%(23/23) and75.0%(9/12) respectively, the difference between the two terms had significant statistic difference (P=0.034).(2) The positive expression rates of Caspase-4in superficial gastritis tissues, intestinal metaplasia, dysplasia and gastric carcinoma were0.0%,43.3%,50.0%and28.6%respectively. The positive expressions of Caspase-4in the teams of superficial gastritis and intestinal metaplasia had significant statistic difference (P=0.001), in the others were not statistically significant (P=0.605, P=0.077). The positive expressions of Caspase-4in the teams of well-differentiated and moderately and poor-differentiated were75.0%(5/8) and14.8%(4/27) respectively, the difference between the two terms had significant statistic difference (P=0.003). The positive expressions of Caspase-4in the teams of gastric carcinoma with lymphatic metastasis and without lymphatic metastasis were13.0%(3/23) and58.3%(7/12) respectively, the difference between the two terms had significant statistic difference (P=0.015).(3) The positive expression rates of NF-KB/p65in superficial gastritis tissues, intestinal metaplasia, dysplasia and gastric carcinoma were0.0%,36.7%,76.7%and65.7%respectively. The positive expressions of NF-KB/p65in the teams of superficial gastritis and intestinal metaplasia had significant statistic difference (P=0.007), also in the the terms of intestinal metaplasia and dysplasia (P=0.002), the other was not statistically significant (P=0.333). The positive expressions of NF-KB/p65in the teams of well-differentiated and moderately and poor-differentiated were25.0%(2/8) and77.8%(21/27) respectively, the difference between the two terms had significant statistic difference (P=0.011). The positive expressions of NF-κB/p65in the teams of phase Ⅰ+Ⅱ and Ⅲ+Ⅳ were14.3%(1/7) and78.6%(22/28) respectively, the difference between the two terms had significant statistic difference (P=0.003). The positive expressions of NF-KB/p65in the teams of gastric carcinoma with lymphatic metastasis and without lymphatic metastasis were87.0%(20/23) and25.0%(3/12) respectively, the difference between the two terms had significant statistic difference (P=0.000).(4) The positive expression rates of Bcl-2in superficial gastritis tissues, intestinal metaplasia, dysplasia and gastric carcinoma were0.0%,33.3%,73.3%and74.3%respectively. The positive expressions of Bcl-2in the teams of superficial gastritis and intestinal metaplasia had significant statistic difference (P=0.012), also in the the terms of intestinal metaplasia and dysplasia (P=0.002), the other was not statistically significant (P=0.931). The positive expressions of Bcl-2in the teams of well-differentiated and moderately and poor-differentiated were25.0%(2/8) and88.9%(24/27) respectively, the difference between the two terms had significant statistic difference (P=0.001). The positive expressions of Bcl-2in the teams of phase I+II and III+IV were28.6%(2/7) and85.7%(24/28) respectively, the difference between the two terms had significant statistic difference (P=0.006). The positive expressions of Bcl-2in the teams of gastric carcinoma with lymphatic metastasis and without lymphatic metastasis were100.0%(23/23) and25.0%(3/12) respectively, the difference between the two terms had significant statistic difference (P=0.000).(5) There was a significant positive correlation between the positive expressions of GRP78and Caspas-4in intestinal metaplasia tissue (P=0.000, r=0.935); There was no significant correlation between the positive expressions of GRP78and Caspas-4in dysplasia and gastric carcinoma. There were a significant negative correlation between the positive expressions of NF-κB/p65and Caspas-4(P=0.007, r=-0.526; P=0.006, r=-0.552; P=0, r=-0.876) and a significant positive correlation between the positive expressions of NF-κB/p65and Bcl-2(P=0.000, r=0.929; P=0.000, r=0.076; P=0.000, r=0.815).Conclusions:(1) There were abnormal expressions of GRP78, Caspase-4, NF-κB/p65and Bcl-2both in gastric carcinoma and precancerous lesions, and it had related with the clinical pathological features of gastric carcinamo.(2) Under the condition of endoplasmic reticulum stress persists, GRP78, Bcl-2, NF-κB/p65, Caspase-4and endoplasmic reticulum stress response may play an important role in the pathogenesis of gastric cancer, it will benefit to detection and treatment of gastric cancer if the indications can be detected in the precancerous stage and to be intervened earlier.