title: 14-3-3sigma in endometrial cancer--a possible prognostic marker in early-stage cancer.
abstract: OBJECTIVE
  We examined expression of 14-3-3sigma, a regulator of cell proliferation, and evaluated its clinical significance in endometrioid endometrial carcinoma.
  
  
  METHODS
  One hundred three endometrioid endometrial adenocarcinoma cases were examined using immunohistochemistry with archival specimens. We correlated this finding with various clinicopathologic variables, including the status of estrogen receptor, progesterone receptor, and MIB-1 (Ki-57).
  
  
  RESULTS
  14-3-3sigma Immunoreactivity was detected in 78 of 103 (75.3%) of carcinoma cases. No statistically significant correlation was detected between status of 14-3-3sigma and any of clinicopathologic variables examined. There was, however, a statistically significant correlation between loss of 14-3-3sigma expression and adverse clinical outcome of the patients (P = 0.0007). In the early stages of cancer (stages I and II), 14-3-3sigma immunoreactivity was absent in 5 of 10 (50.0%) patients who showed recurrence during follow-up, whereas its absence was detected in only 13 of 68 (19.1%) disease-free patients in the same period. In addition, 14-3-3sigma immunoreactivity was absent in 4 of 5 (80.0%) patients who died, whereas its absence was detected in only 14 of 73 (19.2%) patients who had lived during the same period. Patients whose tumors were negative for 14-3-3sigma were at much greater risk to develop recurrent and/or mortal disease (P = 0.0372 and 0.0067). In multivariate analysis using the Cox proportional hazards model, absence of 14-3-3sigma turned out to be statistically independent risk factor in disease-free survival and overall survival even in patients with early-stage disease (P = 0.0321 and 0.0191).
  
  
  CONCLUSIONS
  Results of our study showed that loss or absence of 14-3-3sigma determined by immunohistochemistry may be an important tool to identify endometrial carcinoma cases at high risk of recurrence and/or death, who are otherwise not detected by current clinical and pathologic evaluation, especially in the early stages of the disease. In addition, results of 14-3-3sigma immunohistochemistry in the early stage of endometrial carcinoma could contribute to planning postoperative follow-up and adjuvant therapy.
authors.affiliation: Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan. kito@mail.tains.tohoku.ac.jp
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ito
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Akahira
authors.forename: Michiko
authors.initials: M
authors.lastname: Sakuma
authors.forename: Sumika
authors.initials: S
authors.lastname: Saitou
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okamoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Niikura
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Okamura
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
mesh_terms: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000737:chemistry / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000032:analysis; D005092:Exonucleases / Q000032:analysis*; D005095:Exoribonucleases; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011980:Receptors, Progesterone / Q000032:analysis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D009363:Neoplasm Proteins; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human