PMID- 23162107 OWN - NLM STAT- MEDLINE DCOM- 20130418 LR - 20211203 IS - 1472-4146 (Electronic) IS - 0021-9746 (Linking) VI - 66 IP - 3 DP - 2013 Mar TI - Over-expression of phosphorylated mammalian target of rapamycin is associated with poor survival in oesophageal adenocarcinoma: a tissue microarray study. PG - 224-8 LID - 10.1136/jclinpath-2012-201173 [doi] AB - BACKGROUND: Protein kinase mammalian target of rapamycin (mTOR) is an important downstream effector of the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway. In several tumour types, phosphorylated mTOR (p-mTOR) over-expression is an independent prognostic marker for poor survival. However, p-mTOR expression has not been assessed in oesophageal adenocarcinoma (OAC). MATERIALS AND METHODS: Tumour cores of 154 patients with OAC were included in a tissue microarray (TMA). Scoring criteria were based on p-mTOR staining intensity. RESULTS: 147 (95.5%) patients were available for immunohistochemical evaluation. Over-expression of p-mTOR was detected in 29 (19.7%) tumours, whereas 118 (80.3%) patients showed negative expression. Over-expression was significantly associated with poor overall survival in univariate analysis (HR 1.648; 95% CI 1.019 to 2.664; p=0.042). Median survival was 21.2 months in patients with p-mTOR over-expression and 29.0 in the negative p-mTOR group (p=0.040). In addition, a trend towards p-mTOR over-expression and vasoinvasive growth was seen (p=0.057). In multivariate analysis, including clinical and pathological variables (p<0.10), only T-stage (HR 2.795; 95% CI 1.343 to 5.813; p=0.006) and differentiation grade (HR 2.198; 95% CI 1.353 to 3.570; p=0.001) were independent prognostic markers of poor survival. CONCLUSION: p-mTOR over-expression was detected in 19.7% of patients with OAC and was associated with poor overall survival. FAU - Prins, Margriet J D AU - Prins MJ AD - Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - Verhage, Roy J J AU - Verhage RJ FAU - Ruurda, Jelle P AU - Ruurda JP FAU - ten Kate, Fiebo J W AU - ten Kate FJ FAU - van Hillegersberg, Richard AU - van Hillegersberg R LA - eng PT - Journal Article DEP - 20121116 PL - England TA - J Clin Pathol JT - Journal of clinical pathology JID - 0376601 RN - 0 (Biomarkers, Tumor) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Adenocarcinoma/*metabolism/mortality/secondary MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/metabolism MH - Esophageal Neoplasms/*metabolism/mortality/pathology MH - Female MH - Humans MH - Lymph Nodes/pathology MH - Lymphatic Metastasis MH - Male MH - Middle Aged MH - Netherlands/epidemiology MH - Phosphorylation MH - Prognosis MH - Survival Rate MH - TOR Serine-Threonine Kinases/*metabolism MH - Tissue Array Analysis/methods EDAT- 2012/11/20 06:00 MHDA- 2013/04/20 06:00 CRDT- 2012/11/20 06:00 PHST- 2012/11/20 06:00 [entrez] PHST- 2012/11/20 06:00 [pubmed] PHST- 2013/04/20 06:00 [medline] AID - jclinpath-2012-201173 [pii] AID - 10.1136/jclinpath-2012-201173 [doi] PST - ppublish SO - J Clin Pathol. 2013 Mar;66(3):224-8. doi: 10.1136/jclinpath-2012-201173. Epub 2012 Nov 16.