title: Prognostic implication of TSC1 and mTOR expression in gastric carcinoma.
abstract: BACKGROUND
  Gastric adenocarcinoma is the sixth most common and third most lethal cancer in the world. Except for HER2-targeted therapy, targeted agents against specific molecules participating in gastric carcinogenesis, including those in the mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathway have not been proved to be effective. However, some studies have suggested that dysfunction of TSC1 may augment mTOR inhibitor activity.
  
  
  METHODS
  We studied p-mTOR and TSC1 status by immunohistochemical analysis of gastric carcinoma samples using a tissue microarray method and expression values adopted from The Cancer Genome Atlas.
  
  
  RESULTS
  High p-mTOR and low TSC1 expression status is associated with adverse clinicopathologic parameters. Patients with high p-mTOR levels showed poor survival. Patients with low TSC1 levels showed unfavorable survival status in the overall patients group. The combination of p-mTOR status and TSC1 status provided more strong survival information than using each parameter alone.
  
  
  CONCLUSIONS
  In gastric cancer, high p-mTOR expression level is a statistically significant parameter in multivariate and Kaplan-Meier analyses (log-rank test). In addition to p-mTOR, TSC1 expression provided additional information to predict survival. We therefore suggest that evaluation of both p-mTOR and TSC1 status may be helpful in clinical trials related to mTOR inhibitors.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sun-Ju
authors.initials: SJ
authors.lastname: Byeon
authors.forename: Nayoung
authors.initials: N
authors.lastname: Han
authors.forename: Jiwoon
authors.initials: J
authors.lastname: Choi
authors.forename: Min A
authors.initials: MA
authors.lastname: Kim
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D046888:Tissue Array Analysis; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C000624650:TSC1 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: TSC1; bootstrap analysis; immunohistochemistry; mTOR protein; stomach neoplasms