14-3-3sigma in endometrial cancer--a possible prognostic marker in early-stage cancer.
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.
Ito
Kiyoshi
K
Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan. kito@mail.tains.tohoku.ac.jp
Suzuki
Takashi
T
Akahira
Jun-ichi
J
Sakuma
Michiko
M
Saitou
Sumika
S
Okamoto
Satoshi
S
Niikura
Hitoshi
H
Okamura
Kunihiro
K
Yaegashi
Nobuo
N
Sasano
Hironobu
H
Inoue
Satoshi
S
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
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