title: MCM-2 and MCM-5 expression in gastric adenocarcinoma: clinical significance and comparison with Ki-67 proliferative marker.
abstract: BACKGROUND
  Minichromosome maintenance (MCM) proteins are essential components of DNA replication, being related to cell proliferation, and serve as useful biomarkers for cancer screening, surveillance and prognosis. The aim of the present study was to evaluate the clinical significance of MCM-2 and MCM-5 expression in gastric adenocarcinoma in comparison with Ki-67 proliferative marker.
  
  
  METHODS
  MCM-2, MCM-5 and Ki-67 expression was assessed immunohistochemically in 66 tumoral samples of gastric adenocarcinoma patients and was statistically analyzed in relation to clinicopathological characteristics and patient survival.
  
  
  RESULTS
  MCM-2 expression did not show significant associations with any clinicopathological parameters, while Ki-67 expression was merely significantly associated with tumor size (P = 0.0150). MCM-2 and Ki-67 expression were more frequently in intestinal (median values: 67.5 and 60%) compared to diffuse-type (median values: 60 and 45%) gastric adenocarcinoma cases without though reaching statistical significance (P > 0.05). MCM-5 expression was significantly associated with tumor size (P = 0.0295), presence of lymph node metastases (P = 0.0216) and tumor histopathological stage (P = 0.0098). Patients presenting high MCM-5 expression had significantly shorter survival times (log-rank test, P = 0.0042), whereas neither MCM-2 nor Ki-67 expression showed significant prognostic value (log-rank test, P = 0.9618 and P = 0.7174, respectively). In multivariate analysis, patient age, histopathological stage and grade of differentiation, but not MCM-5 expression, were identified as independent prognostic factors (Cox regression analysis, P = 0.0097, P = 0.0195, P = 0.0035 and P = 0.3245, respectively).
  
  
  CONCLUSIONS
  The present study showed that MCM-5 expression was associated with clinicopathological parameters in gastric adenocarcinoma. However, further studies highlighting the distinct impact of the two histopathological types, intestinal and diffuse, are warranted to delineate whether MCMs could be used as diagnostic and prognostic markers in gastric neoplasia.
authors.affiliation: Department of Forensic Medicine and Toxicology, Medical School, University of Athens, 75 Mikras Asias Street, 11527, Athens, Greece. cgiaginis@yahoo.gr
authors.forename: Constantinos
authors.initials: C
authors.lastname: Giaginis
authors.forename: Athina
authors.initials: A
authors.lastname: Giagini
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Tsourouflis
authors.forename: Elisavet
authors.initials: E
authors.lastname: Gatzidou
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Agapitos
authors.forename: Gregorios
authors.initials: G
authors.lastname: Kouraklis
authors.forename: Stamatios
authors.initials: S
authors.lastname: Theocharis
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; C489423:MCM5 protein, human; D009687:Nuclear Proteins; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2