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01.11.2010 | Head and Neck Oncology | Ausgabe 11/2010

Annals of Surgical Oncology 11/2010

Association of High Levels of Jagged-1 and Notch-1 Expression with Poor Prognosis in Head and Neck Cancer

Zeitschrift:
Annals of Surgical Oncology > Ausgabe 11/2010
Autoren:
MD Jen-Tsun Lin, MD, PhD Mu-Kuan Chen, MD Kun-Tu Yeh, MD Cheng-Shyong Chang, MD Tung-Hao Chang, MS Chi-Yon Lin, MS Yi-Chuan Wu, MS Bi-Wen Su, MD, PhD Kuan-Der Lee, PhD Pey-Jium Chang

Abstract

Background

The aim of this study was to evaluate the prognostic value of the Jagged-1/Notch-1 expression in patients with head and neck carcinoma and to examine the possible role of the Jagged-1/Notch-1 signaling in tumorigenesis.

Methods

Immunohistochemical staining was performed on 59 formalin-fixed, paraffin-embedded head and neck carcinoma surgical specimens for Jagged-1 and Notch-1 expression. The head and neck cancer cell line, Fadu, with or without ectopic expression of the intracellular domain of Notch-1 (NICD) was also used for examining the tumorigenic capacity in vitro and in vivo.

Results

The study included 59 patients with a median age of 54 years (range, 35–73 years). Patients harboring tumors with both high-level Jagged-1 (J1Hi) and high-level Notch-1 (N1Hi) had a worse overall survival than the patients only with J1Hi or N1Hi as well as the patients with low-level Jagged-1 and Notch-1 (J1Lo/N1Lo) (P < 0.001). The 5-year survival rate and the median survival time were 5% and 10.9 months for J1Hi/N1Hi patients, while they were 35.04% and 47.7 months for non-J1Hi/NiHi patients. Ectopic expression of the active Notch-1 (NICD) in Fadu cells greatly enhanced cell migration and invasiveness in vitro and tumorigenic capacity in vivo.

Conclusions

High-level coexpression of Jagged-1 and Notch-1 is associated with poor overall survival in patients with head and neck cancer. Constitutive activation of the Notch signaling, which is possibly initiated by the direct interaction between Jagged-1 and Notch-1 in head and neck cancer, confers tumor cells with a more aggressive phenotype.

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