| Objective: Lesions with serrated structures can be detected in different gastric mucosal lesions,including inflammation,adenoma and adenocarcinoma.Gastric dysplasia(also known as intraepithelial neoplasia)is defined as a neoplastic lesion in the new edition of WHO Digestive System Tumor Classification in 2019,and serrated dysplasia is regarded as a subtype of dysplasia.It is divided into low-grade serrated dysplasia and high-grade serrated dysplasia.This subtype is also known as serrated adenoma.Some studies have found that serrated adenoma has invasive behavior and can rapidly develop into cancer.At present,serrated lesions of digestive tract are common and widely studied in colorectal.There are few studies on gastric mucosal lesions with serrated structures at home and abroad,and most of them are case reports.The clinical significance of serrated dysplasia has not been fully clarified.At present,the study on the immunohistochemical characteristics of the lesions with serrated structure in the stomach is limited to a few serrated adenomas.In order to explore the clinicopathological significance of gastric mucosal lesions with serrated structure,routine morphological observation and immunohistochemical methods were used to analyze the clinicopathological features of chronic inflammation with serrated structure,low-grade serrated dysplasia,high-grade serrated dysplasia and adenocarcinoma with serrated structure,the changes of the expression patterns of mucin MUC1,MUC5 AC,MUC6 and Ki67,and the expression of CDX-2,MLH1 and p53,so as to improve the understanding of the lesions.To provide theoretical basis for clinical diagnosis and treatment.Methods: 1.A total of 108 cases of gastric mucosal lesions with serrated structures underwent biopsy and endoscopic submucosal dissection in the second Hospital of Hebei Medical University from March 2016 to October 2019 were collected,including chronic inflammation(n = 20),low-grade serrated dysplasia(n = 39),high-grade serrated dysplasia(n = 21)and adenocarcinoma(n = 28),Excluding lesions with serrated structures in intestinal metaplasia.2.The gastric mucosal lesions with serrated structures were stained with MUC1,MUC5 AC,MUC6,CDX-2,p53,MLH1 and Ki-67 by immunohistochemical sp method.3.SPSS21.0 statistical software was used for statistical analysis.Chi-square test,Kruskal-Wallis H test and Wilcoxon W test were used to compare the differences of clinical features and immunohistochemical expression of various gastric mucosal lesions with serrated structures,and the relationship between immunohistochemical expression and clinical features.The difference was statistically significant when P < 0.05.Results: 1.Histomorphological and clinicopathological features of gastric mucosal lesions with serrated structure The chronic inflammation with serrated structure showed serrated structure of the fovea epithelium and hyperemia and edema of the lamina propria of the mucosa with lymphocyte and plasma cells infiltration.The histological feature of low-and high-grade serrated dysplasia is that the fovea has a significant serrated shape,usually with micropapilla structure extending to the mucosal surface.Low-grade dysplasia showed mild to moderate atypia,the nucleus was polar and located at the base,mitosis could be seen,and the glandular structure was slightly disordered.High-grade dysplasia showed obvious cell atypia,disappearance of nuclear polarity,large number of abnormal nuclei,enlarged nucleolus,strong basophilia,common mitosis(including pathological mitosis),complex glandular structure,back-to-back,and significant disorder.Adenocarcinoma with serrated structure is characterized by the formation of adenoid serrated structure in the cancer tissue,infiltrating the lamina propria or deeper layer of the mucosa. Among the 20 cases of chronic inflammation with serrated structure,there were 13 males and 7 females,with an average age of 59.00 years(33-84).The median age was 55.50 years old,12 cases were ≤ 60 years old,8 cases were > 60 years old,2 cases were located in cardia,3 cases in basal body and 15 cases in gastric antrum.Among the 39 cases of low-grade serrated dysplasia,there were 32 males and 7 females,with an average age of 58.92 years(41-75).The median age was 61.00 years old,18 cases were ≤ 60 years old,21 cases were > 60 years old,14 cases were located in cardia,9 cases in basal body and 16 cases in gastric antrum.Among the 21 cases of high-grade serrated dysplasia,there were 16 males and 5 females,with an average age of 66.95 years(56-81).The median age was 66.00 years old,≤ 60 years old in 5 cases,> 60 years old in 16 cases,located in cardia(n = 7),basal body(n = 9)and gastric antrum(n = 5).Among the 28 cases of serrated adenocarcinoma,there were 23 males and 5 females,with an average age of 63.89 years(52-82).The median age was 62.00 years old,≤ 60 years old in 9 cases,> 60 years old in 19 cases,located in cardia in 6 cases,basal body in 15 cases,gastric antrum in 7 cases.Chronic inflammation with serrated structure,low-grade and high-grade serrated dysplasia and adenocarcinoma with serrated structure were common in males,and there was no significant difference in sex ratio and age(P > 0.05),while chronic inflammation with serrated structure was most common in gastric antrum,followed by basal body.Low-grade serrated dysplasia is most common in gastric antrum,followed by cardia.High-grade serrated dysplasia is the most common in the basal body,followed by the cardia,and adenocarcinoma with serrated structure is the most common in the basal body,followed by the gastric antrum.There was significant difference in the location of gastric mucosal lesions with serrated structure(P < 0.05).2 Immunohistochemical expression of gastric mucosal lesions with serrated structure 2.1 Expression of MUC1,MUC5 AC,MUC6 and CDX-2 2.1.1Expression of MUC1 In 20 cases of chronic inflammation,MUC1 was positive in 17 cases(85.0%),diffusely expressed in fovea epithelium,of which 14 cases were strongly positive,2 cases were moderately positive and 1 case was weakly positive.In 39 cases of low-grade serrated dysplasia,MUC1 was positive in 37 cases(94.9%),of which 30 cases were diffusely strongly expressed in fovea epithelium,3 cases showed strong positive expression in superficial part of fovea epithelium,weak positive expression in middle and basal part,2 cases showed mottled strong positive expression,1 case showed diffuse moderate positive expression and 1 case of diffuse weak positive expression.MUC1 was positive in all 21 cases of high-grade serrated dysplasia,of which 15 cases were diffusely strongly expressed in fovea epithelium,3 cases were only expressed in superficial part of fovea epithelium,1 case showed strong positive expression in superficial part of foveolar epithelium,1 case showed weak positive expression in middle and basal part,1 case showed diffuse moderate positive expression and 1 case showed diffuse weak positive expression in superficial part of fovea epithelium.MUC1 was positive in all 28 cases of adenocarcinoma,of which 2 cases were diffusely moderately positive and the other 26 cases were diffusely strongly positive.The expression level of MUC1 in adenocarcinoma with serrated structure was significantly higher than that in high-grade serrated dysplasia(P < 0.05).There was no significant difference between chronic inflammation with serrated structure and low-grade serrated dysplasia,and between low-grade serrated dysplasia and high-grade serrated dysplasia(P >0.05).2.1.2 Expression of MUC5 AC MUC5AC was expressed in 19 of 20 cases of chronic inflammation(95.0%),including 17 cases of diffuse strong expression in fovea epithelium,1 case of moderate positive expression and 1 case of mottled strong positive expression.Among the 39 cases of low-grade serrated dysplasia,MUC5 AC was positive in 37 cases(94.9%),of which 30 cases were diffusely strongly expressed in the fovea epithelium,3 cases were moderately positive and 3 cases were mottled strong positive,and 1 case was weakly positive.MUC5AC was positive in all 21 cases of high-grade serrated dysplasia,including 18 cases of diffuse strong expression in fovea epithelium,2 cases of mottled strong positive expression and 1 case of diffuse weak positive expression.In 28 cases of serrated adenocarcinoma,MUC5 AC was positive in 26 cases(92.9%),of which 5 cases were mottled strong positive,and the other 21 cases were diffuse strong positive.There was no significant difference in the expression level of MUC5 AC among all kinds of gastric mucosal lesions with serrated structure(P > 0.05).2.1.3 Expression of MUC6 MUC6 was expressed in serrated structure of chronic inflammation in 7 cases(35.0%),of which 6 cases were strongly positive in small concave base and 1 case was strongly positive in individual fovea epithelium.Of the 39 cases of low-grade serrated dysplasia,15 cases(38.5%)were positive for MUC6,of which 9 cases were strongly positive in the base of the fovea,5 cases were diffusely positive in the epithelium of individual foveoles,and 1 case was strongly and diffusely expressed in the middle and base of the fovea.Of the 21 cases of high-grade serrated dysplasia,9 cases(42.9%)were positive for MUC6,of which 3 cases were strongly positive in the fovea,3 cases were weakly positive in the middle and base of the fovea,2 cases were diffusely positive in the epithelium of individual fovea,and 1 case was weakly and diffusely expressed in the epithelium of the fovea.In 28 cases of serrated adenocarcinoma,MUC6 was positive in 16 cases(57.1%),of which 10 cases were diffuse moderate to strong positive,3 cases were mottled strong positive,1 case was diffuse moderate positive,2 cases were mottled weak positive.There was no significant difference in the expression level of MUC6 among different types of gastric mucosal lesions with serrated structure(P > 0.05).2.1.4 Expression of CDX-2 CDX-2 was positive in 11(55.0%)of 20 cases of chronic inflammation.Among the 39 cases of low-grade serrated dysplasia,31 cases(79.5%)were CDX-2 positive.In 21 cases of high-grade serrated dysplasia,CDX-2 was positive in 14 cases(66.7%).Of the 28 adenocarcinomas with serrated structure,26 cases(92.9%)were positive for CDX-2.The expression level of CDX-2 in low-grade serrated dysplasia was significantly higher than that in chronic inflammation with serrated structure,and that in adenocarcinoma with serrated structure was significantly higher than that in high-grade serrated dysplasia(p < 0.05).There was no significant difference between low-grade serrated dysplasia and high-grade serrated dysplasia(P > 0.05).2.2 Expression of Ki-67 In 20 cases of chronic inflammation,the expression pattern of Ki-67 was expressed in the whole length of the fovea in 9 cases,in the middle and base of the fovea in 6 cases,and in the basal part of the fovea in 5 cases.Among the 39 cases of low-grade serrated dysplasia,13 cases were expressed in the whole length of the fovea,16 cases in the middle and base of the fovea,and 10 cases in the base.Among the 21 cases of high-grade serrated dysplasia,18 cases were expressed in the whole length of the fovea,1 case in the middle and base of the fovea,and 2 cases in the base.The positive expression rate of Ki-67 in chronic inflammation with serrated structure was significantly higher than that in low-grade serrated dysplasia,and that in adenocarcinoma with serrated structure was significantly higher than that in high-grade serrated dysplasia(p < 0.05).There was no significant difference between low-grade serrated dysplasia and high-grade serrated dysplasia(P > 0.05).Of the 21 cases of high-grade serrated dysplasia,4 cases showed asymmetric expression of Ki-67 in the fovea,and MUC6 and Ki-67 showed the same pattern of asymmetric expression in the same fovea,that is,their expressions were highly coincident,and 4 cases of lesions were located in cardia or gastric antrum.Of the 39 cases of low-grade serrated dysplasia,7 cases showed asymmetric expression of Ki-67 in the fovea,but no consistent expression of MUC6 and Ki-67 was found.No asymmetrical expression of Ki-67 was found in the serrated structure of chronic inflammation in 20 cases. 2.3 Expression of MLH1 There was no loss of MLH1 expression in all 108 cases of gastric mucosal lesions with serrated structure.2.4 Expression of P53 The expression of p53 was negative in all 20 cases of chronic inflammation with serrated structure.The positive expression of p53 was found in 9 of 39 cases(23.1%)of low-grade serrated dysplasia.The positive expression of p53 was found in 13 of 21 cases(61.9%)of high-grade serrated dysplasia.Of the 28 cases of serrated adenocarcinoma,20 cases(71.4%)were p53 positive.The positive rate of p53 in high-grade serrated dysplasia was significantly higher than that in low-grade serrated dysplasia(p < 0.05).There was no significant difference between chronic inflammation with serrated structure and low-grade serrated dysplasia,and between high-grade serrated dysplasia and adenocarcinoma with serrated structure(P > 0.05).3 The relationship between the expression of mucin and the location of gastric mucosal lesions with serrated structure.The expression of MUC5 AC in the serrated structure of chronic inflammation was significantly correlated with the location of the disease,and the expression level of MUC5 AC was the highest in the serrated structure of chronic inflammation of gastric antrum.In other types of gastric mucosal lesions with serrated structure,there was no significant correlation between the expression of MUC5 AC and the location of the disease.There was no significant correlation between the expression of MUC1 and MUC6 in various gastric mucosal lesions with serrated structure and the location of the disease.Conclusions: 1.Gastric Chronic inflammation,low-grade and high-grade serrated dysplasia and adenocarcinoma with serrated structure were common in men,in which chronic inflammation and low-grade serrated dysplasia were common in the antrum.High-grade serrated dysplasia and adenocarcinoma were common in the basal body.there was no significant difference in age and sex of gastric mucosal lesions with serrated structure.2.MUC1 and MUC5 AC were strongly expressed in gastric serrated dysplasia,suggesting that gastric serrated dysplasia may originate from gastric fovea epithelium.3.In gastric serrated dysplasia,MUC6 was obviously expressed in the middle and upper part of the fovea,while Ki-67 was asymmetrically expressed in the fovea,and in the same fovea of high-grade dysplasia,MUC6 was asymmetrically expressed in the same pattern as Ki-67,suggesting that the proliferation zone may have shifted upward in serrated dysplasia.4.CDX-2 was expressed in all the four types of lesions with serrated structure,suggesting that the epithelium with this structure had intestinal type differentiation,and the higher the degree of dysplasia of lesions with serrated structure is,the more obvious the intestinal type differentiation is.5.There was no deletion of MLH1 in all kinds of gastric mucosal lesions with serrated structure,and the overexpression rate of p53 protein in serrated dysplasia increased significantly with the increase of the degree of dysplasia,suggesting that the carcinogenesis of gastric mucosal lesions with serrated structure may be related to chromosome instability. |
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