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14-3-3 in Endometrial Cancer–A Possible Prognostic Marker in Early-Stage Cancer

Authors' Affiliations: Departments of ¹ Obstetrics and Gynecology and ² Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan; ³ Research Center for Genomic Medicine and Department of Molecular Biology, Saitama Medical School, Saitama, Japan; and ⁴ Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

Requests for reprints: Kiyoshi Ito, Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai 980-8574, Japan. Phone: 81-22-717-7254; Fax: 81-22-717-7258; E-mail: kito{at}mail.tains.tohoku.ac.jp.

Purpose: We examined expression of 14-3-3, a regulator of cell proliferation, and evaluated its clinical significance in endometrioid endometrial carcinoma.

Experimental Design: 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: 14-3-3 Immunoreactivity was detected in 78 of 103 (75.3%) of carcinoma cases. No statistically significant correlation was detected between status of 14-3-3 and any of clinicopathologic variables examined. There was, however, a statistically significant correlation between loss of 14-3-3 expression and adverse clinical outcome of the patients (P = 0.0007). In the early stages of cancer (stages I and II), 14-3-3 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, 14-3-3 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 14-3-3 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 14-3-3 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 14-3-3 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 14-3-3 immunohistochemistry in the early stage of endometrial carcinoma could contribute to planning postoperative follow-up and adjuvant therapy.