title: Clinical implication of Tiam1 overexpression in the prognosis of patients with serous ovarian carcinoma.
abstract: T lymphoma invasion and metastasis 1 (Tiam1), a guanine nucleotide exchange factor, was originally identified as an invasion- and metastasis-inducing gene in T lymphoma cells. High expression levels of the humanTiam1gene have been found in numerous human malignancies, suggesting a potential role as a modifier of tumor initiation and progression. However, little is known about the status ofTiam1in ovarian carcinoma. The present study aimed to investigate the clinicopathological significance of highTiam1expression in serous ovarian carcinoma. Immunohistochemical staining for Tiam1 was performed in 182 patients with serous ovarian carcinoma, in 76 patients with ovarian borderline tumors and in 72 patients with benign ovarian tumors. Immunofluorescence staining was also performed to detect the subcellular localization of Tiam1 protein in SK-OV-3 ovarian carcinoma cells. The correlations between high Tiam1 expression and the clinicopathological features of the ovarian carcinomas were evaluated by the χ2test and Fisher's exact test. The overall survival (OS) rates were calculated by the Kaplan-Meier method, and the association between prognostic factors and patient survival was analyzed by the Cox proportional hazard model. Tiam1 protein showed a cytoplasmic and nuclear staining pattern in ovarian carcinoma. Strongly-positive Tiam1 protein expression was observed in 59.3% (108/182) of ovarian carcinomas, which was significantly higher than in benign serous tumors (12.5%; 9/72). Moreover, the rate of strongly-positive Tiam1 expression in borderline serous tumors (31.6%; 24/76) was also significantly higher than that in benign serous tumors. High Tiam1 protein expression was closely associated with a high histological grade, metastasis, advanced clinical stage and lower OS rates in ovarian carcinoma. Multivariate analysis indicated that Tiam1 was an independent prognostic factor, along with metastasis and clinical stage, in patients with ovarian carcinoma. In conclusion, Tiam1 expression is strongly associated with grade and outcome in ovarian carcinoma, and may serve as a useful molecular marker for clinical management.
authors.affiliation: Cancer Research Center, Yanbian University, Yanji, Jilin 133002, P.R. China; Department of Pediatrics, Yanbian University Hospital, Yanji, Jilin 133000, P.R. China.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Li
authors.affiliation: Cancer Research Center, Yanbian University, Yanji, Jilin 133002, P.R. China.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Pathology, The People's Hospital of Beijing University, Beijing 100044, P.R. China.
authors.forename: Dingbao
authors.initials: D
authors.lastname: Chen
authors.affiliation: Cancer Research Center, Yanbian University, Yanji, Jilin 133002, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Cancer Research Center, Yanbian University, Yanji, Jilin 133002, P.R. China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Piao
authors.affiliation: Cancer Research Center, Yanbian University, Yanji, Jilin 133002, P.R. China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Cancer Research Center, Yanbian University, Yanji, Jilin 133002, P.R. China.
authors.forename: Guanghai
authors.initials: G
authors.lastname: Yan
authors.affiliation: Department of Pathology, The People's Hospital of Beijing University, Beijing 100044, P.R. China.
authors.forename: Danhua
authors.initials: D
authors.lastname: Shen
keywords: Tiam1; immunohistochemistry; ovarian carcinoma; prognosis; survival analysis