Open Access Maced J Med Sci. 2020 Dec 20; 8(A):947-955. 947 Predictive Value of CDX2 and SOX2 in Chronic Gastritis and Intestinal-type Gastric Cancer Noha Helal 1 *, Zeinab Omran 1 , Tarek Aboushousha 1 , Magdy Youssef 2 , Afkar Badawy 1 , Ayman Abdel Aziz 2 , Mohammed Aboul-Ezz 2 , Mona M. Moussa 1 1 Department of Pathology, Theodor Bilharz Research Institute, Warraq Al Hadar, Giza, Egypt; 2 Department of Hepatology and Gastroenterology, Theodor Bilharz Research Institute, Warraq Al Hadar, Giza, Egypt Abstract BACKGROUND: Worldwide gastric cancer (GC) ranks sixth in incidence and second in mortality among all malignancies. CDX2 has an essential role in the development and maintenance of intestinal diferentiation in the gut and ectopic sites such as intestinal metaplasia (IM) of the stomach. SOX2 contributes to the cell lineages normally found in the stomach, suggesting contribution in gastric diferentiation. AIM: The aim of the study was to assess the expression of CDX2 and SOX2 in chronic gastritis (CG) lesions associated with Helicobacter pylori, IM, or dysplasia as well as in intestinal-type GC. METHODS: Immunohistochemical staining for CDX2 and SOX2 were applied on archival parafn blocks from 80 CG cases, 40 intestinal-type GC cases, and 10 controls. CG cases were either of non-specifc infammation or associated with H. pylori infection. GC cases were of intestinal-type only, excluding any other type of GC. Control cases were of minimal gastritis, negative for H. pylori, IM, and dysplasia. RESULTS: CDX2 expression was correlated with CG associated with H. pylori, IM, and dysplasia as well as with more diferentiated and less invasive pattern of intestinal-type GC, while SOX2 expression was correlated with CG negative for H. pylori and IM as well as with less diferentiated and more invasive intestinal-type GC. CONCLUSION: Both CDX2 and SOX2 could predict the behavior of CG disease over time and plan the suitable line of treatment and both proteins could be potential targets for novel therapeutic interventions. Introduction According to GLOBOCAN 2018 data, the incidence of gastric cancer (GC) ranks sixth and mortality ranks second [1]. Although GC prevalence has shown a continuous reduction since the last mid- century, it is still a common malignancy and a frequent cause of cancer-related deaths [2]. Both histological types of GC: Intestinal and difuse, present distinct morphological, clinical, and epidemiological features and are thought to develop from the activation of independent molecular mechanisms. Intestinal GC develops through a sequence of histological changes, including difuse chronic gastritis (CG), mucosal atrophy, intestinal metaplasia (IM), dysplasia, and fnally invasive carcinoma [3]. Helicobacter pylori are Gram-negative spirochetes which infect more than half of the world’s population, likely due to water contamination and less sanitary living conditions [4]. Infection with H. pylori and the resulting chronic infammation is a major step in the initiation and development of almost 90% of new cases of GC [5]. The pathogenicity of H. pylori is attributed largely to its various virulence components [6]. Chronic infection with H. pylori gives rise to IM which is the most relevant pre-neoplastic lesion of the stomach afecting about 30% of the individuals infected with H. pylori [7]. CDX2 is an intestine-specifc homeobox transcription factor which is expressed in the intestinal epithelial cells from duodenum to the rectum [8] and has an essential role in the development and maintenance of intestinal diferentiation in the gut and ectopic sites such as IM of the stomach and esophagus [9]. It regulates many cellular processes such as cell diferentiation, proliferation, cell adhesion, migration, and tumor genesis [10]. Its role as a prognostic marker in colorectal carcinomas is well known, whereas its role in the outcome of gastric carcinomas is not yet established [11]. SOX2 is a member of the SOX (SRY-related HMG Box) family of transcription factors that play diverse roles, starting from orchestrating the mammalian embryogenesis [12], later on contributing to the normal morphogenesis and homeostasis of the foregut-derived Scientifc Foundation SPIROSKI, Skopje, Republic of Macedonia Open Access Macedonian Journal of Medical Sciences. 2020 Dec 20; 8(A):947-955. https://doi.org/10.3889/oamjms.2020.5570 eISSN: 1857-9655 Category: A - Basic Sciences Section: Pathology Edited by: Sinisa Stojanoski Citation: Helal N, Omran Z, Aboushousha T, Youssef M, Badawy A, Aziz AA, Aboul-Ezz M, Moussa MM. Predictive Value of CDX2 and SOX2 in Chronic Gastritis and Intestinal-type Gastric Cancer. Open Access Maced J Med Sci. 2020 Feb 05; 8(A):947-955. https://doi.org/10.3889/ oamjms.2020.5570. Keywords: CDX2; SOX2; Chronic Gastritis; Gastric Cancer; Helicobacter pylori; Intestinal Metaplasia; Dysplasia *Correspondence: Noha S. Helal, Department of Pathology, Theodor Bilharz Research Institute, El-Nile Street, Warrak El-Hadar, Imbaba, Giza - 12411, Egypt. E-mail: nohasaidhelal@yahoo.com Received: 12-Nov-2020 Revised: 09-Dec-2020 Accepted: 14-Dec-2020 Copyright: © 2020 Noha Helal, Zeinab Omran, Tarek Aboushousha, Magdy Youssef, Afkar Badawy, Ayman Abdel Aziz, Mohammed Aboul-Ezz, Mona M. Moussa Funding: This work was fnanced by TBRI internal project No.114T. Principal investigator: Assistant Prof. Dr. Zeinab Omran. Competing Interests: The authors have declared that no competing interests exist Open Access: This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial 4.0 International License (CC BY-NC 4.0)