| ObjectiveTo investigate the significance and expression of Sox2 and Cdx2 in gastric carcinoma and precancerous lesion,Evision immunohistochemistrical stainning was used to detect the expression of Sox2 and Cdx2 protein in gastric carcinogenesis and precancerous lesion.Analyse the expression of Sox2,Cdx2,MUC5AC,MUC2 and Villin and compared with clinico-pathological features of gasreic carcinoma,explore their roles in progression of gastric carcinoma and their relevant molecular pathological mechanisms.Materials and Methods1.Cilnical PathologyThe material studied which from the oncosurgery,No.1 Hospital of China Medical University,consisted of 257 biopsy specimens from patients 123 female and 134 male patients.The mean age was 60 years(20～80).In 257 cases of gastric carcinoma including 103 cases of intestinal-type gastric carcinoma,130 cases of diffuse-type gastric carcinoma,24 cases of mixed-type gastric carcinoma.The samples contained 205 cases of normal mucosa,127 focal of intestinal metaplasia,100 focal of dysplasia. The carcinoma included 6 cases of papillary adenocarcinoma,19 cases of well-differentiated tubular adenocarcinoma,78 cases of moderately differentiated adenocarcinoma,107 cases of poorly differentiated adenocarcinoma,4 cases of undifferentiated carcinoma,19 cases of signet ring-cell carcinoma,24 cases of mucinous carcinoma;20 cases were in early stage,238 cases were in advanced stage. With lymph node metastasis was found in 176 and 81 cases without lymph node metastasis.None of patients received chemiotherapy or radiotherapy before operation.2.Empirical methodEnvision immunohistochemistry and double staining and HID-ABpH2.5-PAS mucin immunohistochemistry was used to observe the expression with Sox2,Cdx2,MUC2,MUC5AC and Villin in gastric carcinoma and precancerous lesion.the relationships between their expression was analyzed as well.3.Evaluation of stainingSox2 and Cdx2 is located in the nuclei,the positive staining was like brown-yelow granules.MUC2,MUC5AC and Villin is located in cytoplasm.Semi-quantitative integration was used for the evaluation and 2 high magnification visual fields were randomly selected by two observer from each section for observation.The number of positive cells 5%scored 0;6%～25%scored 1;26%～50%scored 2;51%～75%scored 3; and＞75%scored 4.Positive intensity was classified as follows:yellow scored 1, brownish yellow scored 2,and saddle-brown scored 3.After multiplying two integrals, score 0 was as negative expression(-),1～4 as positive expression(+),and 5～8 as moderate expression(++),9～12 as strong positive expression(+++).In the result of mucin staining,the mucin of sulfomucin was stained by brown-stain,the mucin of acetylneuraminic acid was stained by blue-stain,the mucin of neutral was stained by red-stain.4.Statistical AnalysisSPSS 11.5 software was introduced in chi-square test and Kendall's tau-b rank correlation test analysis the relationship between their expressions.Results1.Sox2 and MUC5AC expression level was lower in gastric cancer than that in normal gastric mucosa(P＜0.05).Sox2 MUC5AC expression level was lower in gastric cancer than that in metaplasia and dysplasia(P＜0.05).Sox2 and MUC5AC was less expressed in intestinal carcinoma than that in diffuse carcinoma(P＜0.05)2.Cdx2,MUC2 and Villin expression level was lower in normal gastric mucosa than that in gastric carcinoma(P＜0.05).Cdx2,MUC2 and Villin expression level was lower in gastric cancer than that in metaplasia and dysplasia(P＜0.05).Cdx2,MUC2 and Villin was expressed in intestinal carcinoma more than that in diffuse carcinoma(P＜0.05).3.Sox2 showed positive expression of histological classification,invasive depth and lymphnode metastasis(P＜0.05).MUC5AC was closely correlated with man sex,lymph node metastasis and invasive drpth(P＜0.05).MUC2 is correlated with histological classification,invasive depth and Borrmannn classification(P＜0.05).Villin was associated invasive depth and histological classification(P＜0.05).4.In gastric carcinoma,Sox2 expression was associated with MUC5AC expression, and so with the expression with Cdx2 and MUC2/Villin(P＜0.05).But Sox2 expression was negatively correlated with Cdx2 expression.Conclusions1.Sox2 expression is progressively decreased in normal gastric mucosa,intestinal metaplasia,dysplasia and cancer.Sox2 may play an important role in maintaining a gastric phenotype in normal gastric epithelium.Sox2 was less expressed in intestinal carcinoma than that in diffuse carcinoma.The results suggest that the expression of Sox2 maybe closely associated with diffuse type carcinoma.2.Cdx2 expression is the highest in intestinal metaplasia,the result suggest that Cdx2 may play an important role in maintaining the intestinal phenotype.Cdx2 expressed in intestinal carcinoma more than that in diffuse carcinoma Cdx2 maybe closely correlated with intestinal type carcinoma.3.Sox2 and Cdx2 are inversely related that suggests Sox2 and Cdx2 could thus be an important mechanism in IM and the development of gastric carcinoma.
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