title: Expression of phosphorylated Akt, mTOR and MAPK in type I endometrial carcinoma: clinical significance.
abstract: OBJECTIVE
  The Akt/mTOR and MAPK pathways are frequently activated in various tumor types but data on endometrial carcinoma are limited. The aim of the present study was to investigate the clinical significance of the expression of phosphorylated MAPK, Akt and mTOR (p-MAPK, p-Akt, p-mTOR) in type I endometrial carcinoma.
  
  
  METHODS
  The study comprised of 103 formalin-fixed paraffin-embedded (FFPE) type I endometrial carcino ma cases, retrospectively retrieved and assessed by immuno histochemistry for p-MAPK, p-Akt and p-mTOR expression. The expression of these proteins was also studied in non-neoplastic endometrial tissue adjacent to the tumor.
  
  
  RESULTS
  The expression patterns of these molecules differed between malignant and non-tumorous tissue specimens. The immuno reactivity for p-Akt was exclusively detected in the neoplastic tissues. Expression levels of p-MAPK were higher in tumors compared to non-neoplastic endometrium (p<0.001), while p-mTOR was found to be over-expressed in non-neo plastic endometrium compared to carcinomas (p=0.001). Expression of p-Akt was correlated with p-MAPK protein levels (p=0.022, r=0.229). On the other hand, no association was found with clinicopathological parameters and with disease-free (DFS) or overall survival (OS) of the patients.
  
  
  CONCLUSIONS
  Our findings support the de-regulation of the PI3K/Akt/mTOR and MAPK signaling pathways in type I endometrial carcinomas suggesting involvement of these pivotal pathways in endometrial carcinogenesis.
authors: Department of Pathology, University Hospital, University of Patras School of Medicine, Patras, Greece.
authors: Helen P
authors: HP
authors: Kourea
authors: Department of Obstetrics-Gynecology, University Hospital, University of Patras School of Medicine, Patras, Greece nikolaoumarinos@yahoo.gr.
authors: Marinos
authors: M
authors: Nikolaou
authors: Department of Pathology, University Hospital, University of Patras School of Medicine, Patras, Greece.
authors: Vasiliki
authors: V
authors: Tzelepi
authors: Department of Obstetrics-Gynecology, University Hospital, University of Patras School of Medicine, Patras, Greece.
authors: Georgios
authors: G
authors: Adonakis
authors: Department of Radiation Oncology and Stereotactic Radiotherapy, University Hospital, University of Patras School of Medicine, Patras, Greece.
authors: Dimitrios
authors: D
authors: Kardamakis
authors: Department of Obstetrics-Gynecology, University Hospital, University of Patras School of Medicine, Patras, Greece.
authors: Vasilios
authors: V
authors: Tsapanos
authors: Department of Pathology, University Hospital, University of Patras School of Medicine, Patras, Greece.
authors: Chrisoula D
authors: CD
authors: Scopa
authors: Department of Oncology, University Hospital, University of Patras School of Medicine, Patras, Greece.
authors: Charalambos
authors: C
authors: Kalofonos
authors: Department of Obstetrics-Gynecology, University Hospital, University of Patras School of Medicine, Patras, Greece.
authors: Georgios
authors: G
authors: Decavalas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000096:biosynthesis*; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis; D010766:Phosphorylation; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D012189:Retrospective Studies; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis*
chemical_list: D020929:Mitogen-Activated Protein Kinase Kinases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human
keywords: Type I endometrial carcinoma; clinicopathological factors; p-Akt; p-MAPK; p-mTOR; prognosis