title: Tight junction protein claudin 4 in gastric carcinoma and its relation to lymphangiogenic activity.
abstract: OBJECTIVE
  Gastric cancer is the second most common cause of cancer-related death worldwide. Claudins are a family of tight junction proteins that are biologically relevant in many cancer progression steps. This study aimed to investigate the expression of the intestinal claudin (claudin 4) in gastric carcinoma and to evaluate its relation to the different clinicopathologic prognostic parameters, especially lymphangiogenesis (production of new lymphatic vessels, measured by lymphovascular density (LVD)) and lymphovascular invasion (LVI).
  
  
  METHODS
  Fifty-five gastric carcinoma specimens were immunohistochemically stained for claudin 4 and D2-40 (for detection of lymphatic vessel endothelium).
  
  
  RESULTS
  High expression of claudin 4 was detected in 26 of 55 (47.3%) cases. Low expression of claudin 4 was related to poorly differentiated type (p=0.001), non-intestinal (diffuse) type (p=0.001), deeper tumour invasion (p<0.001), lymph node metastasis (p=0.001), and higher stage (p=0.001). In addition, higher LVD was related to poorly differentiated types (p=0.001), non-intestinal type (p=0.001), lymph node metastasis (p=0.015), and higher tumour, node, metastasis (TNM) stage (p=0.001). LVI was related to lymph node metastasis (p=0.025), higher TNM stage (p=0.001), and LVD (p=0.001). Claudin 4 significantly correlated with both LVD (p=0.009) and LVI (p=0.009).
  
  
  CONCLUSIONS
  High expression of claudin 4 was associated with the more differentiated intestinal-type gastric carcinoma and lost in poorly differentiated diffuse type. So, claudin 4 may be used as one of the differentiating markers between the two major types of gastric carcinoma (intestinal vs. diffuse). LVD and LVI were related to higher incidence of lymph node metastasis and therefore could be used as predictive markers for lymph node metastasis in limited specimens during early gastric carcinoma to determine the need for more invasive surgery. Low expression of claudin 4 was related to lymphangiogenesis. This may shed light on the relation of tight junction protein expression and lymphangiogenesis.
authors.affiliation: Department of Pathology, Tanta University, Egypt. Electronic address: mmshareef73@gmail.com.
authors.forename: Mohamed Moustafa
authors.initials: MM
authors.lastname: Shareef
authors.affiliation: Department of Pathology, Tanta University, Egypt.
authors.forename: Dina Mohammed Adel
authors.initials: DM
authors.lastname: Radi
authors.affiliation: Department of Pathology, Tanta University, Egypt.
authors.forename: Asmaa Mustafa Mohammed
authors.initials: AM
authors.lastname: Eid
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D062506:Claudin-4 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; C568157:CLDN4 protein, human; D062506:Claudin-4; C500987:monoclonal antibody D2-40
keywords: Claudin 4; D2-40; Gastric carcinoma; Lymphangiogenesis