Published Online First: 5 July 2006. doi:10.1136/jcp.2006.039099
Journal of Clinical Pathology 2007;60:510-514
Copyright © 2007 by the BMJ Publishing Group Ltd & Association of Clinical Pathologists.
Upregulation of Twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis
Hiu-Fung Yuen1,
Yuen-Piu Chan1,
Michelle Lok-Yee Wong1,
Wei-Kei Kwok2,
Ka-Kui Chan1,
Pin-Yin Lee3,
Gopesh Srivastava1,
Simon Ying-Kit Law3,
Yong-Chuan Wong2,
Xianghong Wang2,
Kwok-Wah Chan1
1 Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
2 Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
3 Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
Correspondence to:
Dr K-W Chan
Department of Pathology, The University of Hong Kong, Pokfulam, Hong Kong, China; kwchan{at}pathology.hku.hk
Background: The antiapoptotic and epithelialmesenchymal transition activities of Twist have been implicated in the neoplastic transformation and the development of metastasis, respectively. Upregulation of Twist, described in several types of human cancer, also acts as a prognostic marker of poor outcome.
Aim: To investigate Twist expression in oesophageal squamous cell carcinoma (SCC) and its prognostic value in a Chinese cohort of patients with oesophageal SCC.
Methods: Twist expression in primary oesophageal SCC of 87 Chinese patients was investigated by immunohistochemical staining. Twist protein level in one immortalised normal oesophageal epithelial cell line and six oesophageal SCC cell lines was measured by western blot analysis. Twist mRNA level in 30 pairs of frozen specimens of primary oesophageal SCC and non-neoplastic oesophageal epithelium from the upper resection margin of corresponding oesophagectomy specimen was also determined by semiquantitative reverse transcription-PCR.
Results: It was found that Twist was upregulated in oesophageal SCC cell lines, and its mRNA and protein levels were both increased in oesophageal SCC and the non-neoplastic oesophageal epithelium (p<0.001). In addition, a high level of Twist expression in oesophageal SCC was significantly associated with a greater risk for the patient of developing distant metastasis within 1 year of oesophagectomy (OR 3.462, 95% CI 1.201 to 9.978; p = 0.022).
Conclusions: Our results suggest that upregulation of Twist plays a role in the neoplastic transformation to oesophageal SCC and subsequent development of distant metastasis. Twist may serve as a useful prognostic marker for predicting the development of distant metastasis in oesophageal SCC.
Abbreviations: EMT, epithelialmesenchymal transition; FBS, fetal bovine serum; RT-PCR, reverse transcription-PCR; SCC, squamous cell carcinoma
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H.-W. Lo, S.-C. Hsu, W. Xia, X. Cao, J.-Y. Shih, Y. Wei, J. L. Abbruzzese, G. N. Hortobagyi, and M.-C. Hung
Epidermal Growth Factor Receptor Cooperates with Signal Transducer and Activator of Transcription 3 to Induce Epithelial-Mesenchymal Transition in Cancer Cells via Up-regulation of TWIST Gene Expression
Cancer Res.,
October 1, 2007;
67(19):
9066 - 9076.
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Copyright © 2007 by the BMJ Publishing Group Ltd & Association of Clinical Pathologists.