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Prognostic Significance of Jab1 Expression in Laryngeal Squamous Cell Carcinomas

¹ Department of Cell Physiology, Faculty of Medicine, Kagawa University, Kagawa, Japan and ² Department of Otolaryngology, The First Affiliated Hospital of China Medical University, Shenyang, China

Requests for reprints: Masaaki Tokuda, Department of Cell Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-Gun, Kagawa, 761-0793, Japan. Phone: 87-891-2095; Fax: 87-891-2096; E-mail: tokuda{at}med.kagawa-u.ac.jp.

Purpose: Jun activation domain-binding protein 1 (Jab1) is known as a coactivator of AP1 transcription factor, which contributes to tumor progression by degrading the p27^kip1 protein. The purpose of this study is to investigate whether Jab1 expression is correlated with p27^kip1 level and cell proliferation, as well as whether Jab1 expression is associated with clinicopathologic variables and prognosis of laryngeal squamous cell carcinoma (LSCC).

Experimental Design: Immunohistochemical and/or Western blot analysis was done in HEp-2 cells and 102 cases of LSCCs.

Results: Jab1 expression was negatively associated with p27^kip1 expression and was positively associated with cell proliferation both in HEp-2 cells and LSCCs. Jab1 overexpression was detected in 51% LSCCs and was significantly associated with unfavorable clinicopathologic variables. Survival analysis revealed that Jab1 overexpression is significantly associated with short disease-free and overall survival (P = 0.0036 and P = 0.0001, respectively). When Jab1 and p27^kip1 are combined, patients with Jab1(+)/p27^kip1(–) revealed poor disease-free and overall survival (P= 0.0008 and P < 0.0001, respectively). When Jab1 expression and lymph node status are combined, patients with Jab1(+)/lymph node(+) revealed poorer disease-free andoverall survival than others (P < 0.0001 and P < 0.0001, respectively). Furthermore, patients with the phenotype of Jab1(+)/p27^kip1(–)/lymph node(+) revealed the worst disease-free and overall survival (P < 0.0001 and P < 0.0001, respectively). Multivariate analysis revealed that Jab1 protein is an independent prognostic indicator for overall survival.

Conclusions: These findings suggested that Jab1 protein may contribute to the tumor progression and represent a novel prognostic indicator for LSCCs.

Key Words: Jab1 • larynx • Squamous cell carcinoma

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