title: High EpCAM expression is linked to proliferation and lauren classification in gastric cancer.
abstract: BACKGROUND
  The association of EpCAM expression with the progression of gastric cancer remains unclear. Here, we investigated the expression of EpCAM in gastric cancer subtypes and correlated the data to tumor cell proliferation and clinicopathologic factors.
  
  
  METHODS
  The intratumoral expression of EpCAM was assessed in 163 primary gastric cancers (61 diffuse-, 62 intestinal-, 32 mixed-type and 8 unclassified tumors) by immunohistochemistry, using the monoclonal antibody Ber-EP4. Intensity of staining was classified according the HercepTest-score using a standardized scoring system. Ki-67 was used to examine the proliferation in tumor tissue.
  
  
  RESULTS
  Strong EpCAM expression was observed in 77% of the tumors and in 85% of the corresponding lymph nodes. Of the primary tumors, 58% (n=74) presented a homogeneous intratumoral EpCAM expression while 42% were characterised by a heterogenous expression pattern. Tumors with high EpCAM expression at the invasive front were associated with significantly (p=0.03) higher proportion of lymph node metastases and lower median overall survival (p=0.001). Diffuse type tumors presented a significantly higher EpCAM expression at the invasion front compared with the tumor centre (p=0.036). Multivariate survival analysis identified high EpCAM expression at the invasive front as an independent prognostic factor.We observed a significant (p=0.001) correlation between high EpCAM expression and higher tumor cell proliferation.
  
  
  CONCLUSIONS
  High EpCAM expression associates with proliferation and progression of gastric cancer, especially in the diffuse type. Considering the discontenting results of the current adjuvant concepts for gastric cancer patients, EpCAM might be target in the adjuvant therapy of this malignant disease.
authors.affiliation: Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Feride
authors.initials: F
authors.lastname: Kroepil
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Dulian
authors.forename: Daniel
authors.initials: D
authors.lastname: Vallböhmer
authors.forename: Helene
authors.initials: H
authors.lastname: Geddert
authors.forename: Andreas
authors.initials: A
authors.lastname: Krieg
authors.forename: Christian
authors.initials: C
authors.lastname: Vay
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Topp
authors.forename: Jan Schulte
authors.initials: JS
authors.lastname: am Esch
authors.forename: Stephan E
authors.initials: SE
authors.lastname: Baldus
authors.forename: Olivier
authors.initials: O
authors.lastname: Gires
authors.forename: Wolfram T
authors.initials: WT
authors.lastname: Knoefel
authors.forename: Nikolas H
authors.initials: NH
authors.lastname: Stoecklein
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D049109:Cell Proliferation; D000071858:Epithelial Cell Adhesion Molecule; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008207:Lymphatic Metastasis; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D019394:Ki-67 Antigen