title: [Correlations of p-AKT with PTEN, P53, HER-2 expressions in endometrial carcinoma and their relationship with patient survival].
abstract: OBJECTIVE
  To investigate the correlation of phosphorylated protein kinase B(p-AKT) with phosphatase and tensin homolog(PTEN), P53,human epidermal growth factor receptor 2(HER-2) expressions in endometrial carcinoma and their significance.
  
  
  METHODS
  The expressions of p-AKT with PTEN, HER-2, P53 and Ki67 were assessed in 95 endometrial carcinomas using immunohistochemistry. The biomarker expressions correlated with clinicopathologic variables and with patient survival.
  
  
  RESULTS
  (1) p-AKT was positive in 53.7% (51/95) of tumors and was found to express almost similarly in endometrioid adenocarcinoma(EC) and non-enometrioid adenocarcinoma (NEC). There was no significant difference of patient survival between p-AKT positive and negative subgroups (P=0.757). (2) PTEN loss was found in 56.8%(54/95) of tumors, and occurred more often in EC(60.7%, 51/84) than in NEC (27.3%, 3/11), which was of statistical significance (P=0.035). The patients with PTEN loss had a longer survival than those without (P=0.015). (3) Although there was no significant correlation between p-AKT and PTEN expression, the extended analysis showed that the predictive value of PTEN loss in p-AKT positive subgroup (P=0.148) was lower than that in p-AKT negative expression subgroup (P=0.055). Meanwhile p-AKT positive and PTEN loss might have synergic effect on tumor proliferation, Ki67 positive rate was highest in PTEN+/p-AKT+ subgroup (40.0%) and lowest in PTEN-/p-AKT- subgroup (8.7%), which was of significant difference (P=0.015). (4) No correlation was found between p-AKT expression and P53 or HER-2 status (P>0.05). On the other hand, HER-2 and P53 positive correlated significantly (r=0.209, P=0.041) and occurred more frequently in NEC (45.5%, 100.0%) than in EC(6.0%, 42.9%)(P <0.05), which were found to predict poor survival (P<0.05).
  
  
  CONCLUSIONS
  p-AKT was activated equally in EC and NEC. p-AKT positive alone might have limited effect on patient survival, however, p-AKT expression might lower the predictive value of PTEN loss in endometrial carcinoma. Moreover, p-AKT positive and PTEN loss might have synergic effect on tumor proliferation. On the other hand, as p-AKT expression did not have any correlations with PTEN, P53 and HER-2 status in this cohort, there might be other important factors involved in p-AKT activation in endometrial carcinoma. In sum, further investigation should be conducted in the targeted therapy based on p-AKT and associated molecular mechanism in advanced endometrial carcinoma.
authors.affiliation: Department of Pathology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Xiao-ming
authors.initials: XM
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.forename: Ying
authors.initials: Y
authors.lastname: Dong
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yi-ting
authors.initials: YT
authors.lastname: Meng
authors.forename: Ting
authors.initials: T
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000378:metabolism* / Q000601:surgery; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000601:surgery; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000601:surgery; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D019394:Ki-67 Antigen; D051059:PTEN Phosphohydrolase; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C495901:TP53 protein, human; C508053:ERBB2 protein, human; C494918:AKT1 protein, human; C494929:PTEN protein, human