Assessment Of Helicobacter Pylori Association With Expression Of CDX2 In Gastric Intestinal Metaplasia

Introduction Gastric cancer and its preceding lesions are highly prevalent in China.Gastric intestinal metaplasia,an intermediate lesion in the development of intestinal-type gastric cancer and a well-established precancerous lesion,is observed in the milieu of long standing non-atrophic gastritis and atrophic gastritis.However,not all patients with this lesion would certainly develop gastric carcinoma – and thus,biological and genetic pathogenesis of GIM and underlying mechanism of its progression into a carcinoma are still not completely understood.Most of the patients with GIM remain asymptomatic.AG and GIM are usually diagnosed at endoscopy in East Asian countries while histological examination of biopsy obtained during endoscopy is a necessity for diagnosis in the western countries.Helicobacter pylori is a wellestablished cause for the development of gastric precancerous lesions and gastric cancer.Subjects carrying Helicobacter pylori(H.pylori),in their stomach,are at high risk for developing gastric carcinoma.Thus,H.Pylori is designated as Class I carcinogen by the International Agency for Research on Cancer on the World Health Organization.Countries with a higher prevalence of Helicobacter pylori infection and gastric cancer also have a high tendency of being prevalent for AG and GIM.Caudalrelated homeobox transcription factor 2(CDX2),a member of the caudal-related homeobox gene family,is involved in the early differentiation and maintenance of the intestinal epithelial cell during gastrointestinal development.Aberrant expression of CDX2 in human GIM and atrophic gastritis has been extensively reported in the literature but it has also been proposed that CDX2 expression may play a tumor suppressor role rather a progressive role in the development of advanced cancer.Thus,further studies demonstrating the role of CDX2 involvement in progression or downregulation in gastric carcinogenesis are needed.H.pylori has also been reported to be the causative agent for the expression of CDX2 in gastric mucosa,though,the underlying mechanisms are yet to be identified.Objective In the present study,the aim was to establish the role of H.pylori to induce gastric expression of CDX2 in gastric intestinal metaplasia.In addition,expression of CDX2 in atrophic gastritis,GIM,dysplasia and gastric cancer was also evaluated.Design,Place and duration of Study 62 biopsies – resected at endoscopy between August 2016 and January 2017 – were selected for further evaluation from the Department of Pathology,The First Hospital of Jilin University,Changchun,China.Patients and Methods The study inducted 32 cases of GIM and 10 cases each of atrophic gastritis,dysplasia and gastric cancer.Data including age,gender,and pathology reports were retrieved from electronic medical records.The Ethics Committee of our hospital approved the study.CDX2 expression was evaluated using immunohistochemistry.In order to observe CDX2,antigen conditions were retrieved by treating the slides in 0.01mol/L EDRA,p H 9.0 in a microwave oven for three minutes.Immunohistochemical staining was performed using CDX2(clone EP125;ZSGB Biotechnology Co.,Bei Jing,China).Fisher’s exact test was used for the analysis of the data collected.A P value of less than 0.05 was considered to be statistically significant.Results Of the 62 patients inducted in the study,CDX2 expression was observed in 53(85.5%).Mean age of these patients was 59 years(s.d.:11.3;range: 38-87)and included 60.38% male(32/53)and 39.62% female(21/53).However,age and gender were not found to be significantly associated with expression of CDX2(P>0.05).CDX2 was highly expressed in individuals with IM(90.6%).8 out of 10 in each-AG,dysplasia and cancer groups-stained positive for CDX2.There was no statistical significant difference for expression of CDX2 among the groups(P=0.714).Most of the patients with IM(CDX2 positive)were male(17/29)as compared to female(12/29).However,the difference was not statistically significant(P =0.57).Only 8 out of 29 IM CDX2 positive specimens tested positive for H.pylori(P=1.0).Conclusion In the present study,CDX2 expression was investigated in the gastric precancerous lesions and gastric cancer.Correlation between age,gender and CDX2 expression was also assessed.Firstly,CDX2 was highly expressed in GIM(90.6%).Secondly,the study found uniform prominent expression of CDX2 in GIM,dysplasia and gastric cancer highlighting the progressive role of CDX2 in the gastric carcinogenesis.A low prevalence of H.pylori was observed in GIM samples.Thus,putting together,our study showed that CDX2 expression is highly expressed in gastric precancerous lesions and gastric cancer and maybe regarded as an oncogene.Age,gender and H.pylori were not found to be associated with expression of CDX2 in GIM.Further studies should be conducted to identify the risk factors – genetic and environmental-that are involved in the development of intestinal differentiation as well as progression to gastric oncogenesis that would aid in identifying the high risk group.