title: MKK4 status predicts survival after resection of gastric adenocarcinoma.
abstract: OBJECTIVE
  Lack of expression of the tumor-suppressor gene MKK4 is significantly correlated with poor survival after resection of gastric adenocarcinoma.
  
  
  METHODS
  Retrospective review of medical records after construction and immunolabeling of tissue microarrays for clinical correlation.
  
  
  METHODS
  The Johns Hopkins Hospital, Baltimore, Md.
  
  
  METHODS
  Patients operated on because of gastric adenocarcinoma between 1983 and 1995. Main Outcome Measure Long-term survival and MKK4 status.
  
  
  RESULTS
  Primary tumors (N = 124) were scored as 0 (no labeling), 1+ (weak labeling), or 2+ (strong labeling) in 9 (7%), 80 (65%), and 35 (28%) patients, and 5-year survival in these patients was 0%, 21%, and 28%, respectively. Given the small size (7%) of the MKK4-negative group (as expected, given the 5%-10% incidence of genetic loss in carcinomas), a Cox proportional hazards analysis was performed, adjusting for age, sex, and tumor stage. This multivariate analysis revealed a 5-fold increased risk of death (P<.001) in patients whose primary tumors were MKK4-negative. Furthermore, the addition of MKK4 status significantly improved the Cox model, changing log likelihood from -1410 to -369, confirming that MKK4 status was truly the effector of the survival difference and not a bystander.
  
  
  CONCLUSIONS
  The lack of expression of the tumor-suppressor gene MKK4 in resected gastric adenocarcinoma is robustly associated with poor survival. This finding may provide a useful prognostic tool in patients with gastric adenocarcinoma.
authors.affiliation: Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21231-1000, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Cunningham
authors.forename: Farin
authors.initials: F
authors.lastname: Kamangar
authors.forename: Min P
authors.initials: MP
authors.lastname: Kim
authors.forename: Sommer
authors.initials: S
authors.lastname: Hammoud
authors.forename: Raqeeb
authors.initials: R
authors.lastname: Haque
authors.forename: Christine
authors.initials: C
authors.lastname: Iacobuzio-Donahue
authors.forename: Raheela
authors.initials: R
authors.lastname: Ashfaq
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kern
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: Richard E
authors.initials: RE
authors.lastname: Heitmiller
authors.forename: Michael A
authors.initials: MA
authors.lastname: Choti
authors.forename: Keith D
authors.initials: KD
authors.lastname: Lillemoe
authors.forename: John L
authors.initials: JL
authors.lastname: Cameron
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Yeo
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Montgomery
authors.forename: Richard D
authors.initials: RD
authors.lastname: Schulick
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D000368:Aged; D016009:Chi-Square Distribution; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D048670:MAP Kinase Kinase 4 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D015996:Survival Rate
chemical_list: D048670:MAP Kinase Kinase 4