Expression Of SHP-1 And EGFR In Human Adenocarcinoma Of Gastric Cardia

Objective: The morbility of adenocarcinoma of gastric cardia shows an increased tendency in this rencent years. The lower diagnosis rate made its prognosis was very bad. Further research about the mechanism of this carcinoma needed to be done to improve the effect of treatments. In this study, the expression of SHP-1 and EGFR had been evaluated in normal gastric mucosa, paraneoplastic gastric mucosa and adenocarcinoma tissue of gastric cardia, and their correlation had been analyzed too. It was expected to explain their roles in tumorigenesis, progression and metastasis of human cardiac adenocarcinoma.Methods: 1 Immunohistochemistry methods were used to detect the expression of SHP-1 and EGFR protein in 86 cases of cardia adenocarcinoma patients'tumor tissue, paraneoplastic gastric mucosa and normal gastric mucosa.2 SPSS 13.0 software was applied to analyze the results of all experiments.Results: 1 The positive staining rates of SHP-1 in normal gastric mucosa, paraneoplastic gastric mucosa and adenocarcinoma tissue showed a decrease tendency. There was statistical significance in 3 groups (P<0.01). Further analysis indicated that each group of the normal or paraneoplastic gastric mucosa was obviously higher than the adenocarcinoma tissue group (P<α′). On the contrary, the expression of EGFR showed an increased tendency in 3 groups. It had a noticeable difference in each 2 groups (p<0.05). The Spearman rank correlation analysis method was used to analyze the correlation of SHP-1 and EGFR in 3 groups. It showed that the expression of SHP-1 was negative related to the EGFR's in normal gastric mucosa group (r=-0.389, p<0.01) and adenocarcinoma tissue goup (r=-0.593, p<0.01), but in paraneoplastic gastric mucosa group, they were uncorrelated (r=-0.211, p>0.05).2 In normal gastric mucosa group, the difference of SHP-1 and EGFR's expression were no statistical significance among all the clinical and pathological parameters (p>0.05).3 In paraneoplastic gastric mucosa group, the positive stain rate of SHP-1 in I/II grade of differentiation group (30/55, 54.5%) showed much more than that of grade III group (9/31, 29.0%), P<0.05. The positive rate of EGFR in grade I (2/15, 13.3%) was less than that of in grade III (18/31, 58.1%), P=0.004. And when lymph metastasis was concered, SHP-1 expression in paraneoplastic gastric mucosa with lymph metastasis (17/49, 34.7%) were lower than those without lymph metastasis (22/37, 59.5%), P<0.05. But the rate of EGFR in paraneoplastic gastric mucosa with lymph metastasis (24/49, 49.0%) were much higher than those without lymph metastasis (10/37, 27%), P<0.05. The expression of SHP-1 and EGFR was not correlated with other parameters. 4 In adenocarcinoma tissue group, the expression of SHP-1 in I/II grade of differentiation group (20/55, 36.4%) were higher than that of in grade III group (4/31, 12.9%), p<0.05. The positive stain rates of EGFR in grade III group (24/31, 77.4%) were obviously higher than that of grade I group (5/15, 33.3%), p<0.01. The positive stain rate of EGFR in adenocarcinoma tissue with lymph metastasis group (37/49, 75.5%) was much higher than in without lymph metastasis group (14/37, 37.8%), P<0.01. In TNM stage groups, the rate of EGFR in stage III/IV group (39/51, 76.5%) were higher than those of in stage I/II group (12/35, 34.3%), P<0.01. The expression of SHP-1 and EGFR was not correlated with invasion depth, tumor size, tumor embolus in vessel, age, sex and cigarette use index.Conclusions: 1 The positive stain rate of SHP-1 in carcinoma tissue group was obviously lower than that in paraneoplastic and normal gastric mucosa group. It indicated that the deactivation of SHP-1 gene was involved in tumorigenesis in adenocarcinoma of human gastric cardia.2 In paraneoplastic gastric mucosa and adenocarcinoma tissue group, the expression of SHP-1 in well/moderately differentiated adenocarcinoma group were higher than that of poorly differentiated group, in without lymph metastasis group were higher than those with lymph metastasis group. These results indicated that the rate of SHP-1 gene expression descend was correlated with the malignant phenotype and lymphatic metastasis of cardia adenocarcinoma. 3 The expression of EGFR in adenocarcinoma tissue was obviously higher than that in paraneoplastic and normal gastric mucosa. It suggests that the EGFR over expression play an important role in tumorigenesis of cardia carcinoma.4 The expression of EGFR in adenocarcinoma tissue group was correlated with pathological classification, lymphatic metastasis and clinical stage. It showed that EGFR overexpression was related to the malignant phenotype, metastasis and prognosis of cardia carcinoma.5 The positive stain rate of SHP-1 was negative related to the EGFR's in normal gastric mucosa group and adenocarcinoma tissue goup, which indicated that the SHP-1 gene silence was related to the proto-oncogene c-erbB-1 overexpressed in the process of the normal gastric mucosal epithelial cell's canceration. These data support the possibility that the SHP1 gene is one of the tumor suppressor genes.