Korean J Pathol.  2014 Aug;48(4):283-291. 10.4132/KoreanJPathol.2014.48.4.283.

The Role of TWIST in Ovarian Epithelial Cancers

• Kim K
• Park EY
• Yoon MS
• Suh DS
• Kim KH
• Lee JH
• Shin DH
• Kim JY
• Sol MY
• Choi KU

• KMID: 1719562
• DOI: http://doi.org/10.4132/KoreanJPathol.2014.48.4.283

Abstract

BACKGROUND
Epithelial-mesenchymal transition (EMT) is associated with tumor hypoxia. EMT is regulated, in part, by the action of TWIST, which inhibits of E-cadherin expression and may interfere with the p53 tumor-suppressor pathway.
METHODS
We examined the expression of TWIST, E-cadherin, hypoxia-inducible factor 1alpha (HIF1alpha), and p53 by immunohistochemistry in 123 cases of ovarian epithelial cancers (OEC) to evaluate the role of TWIST in OEC. We assessed the association between protein expression and clinicopathologic parameters.
RESULTS
The expression of TWIST, E-cadherin, HIF1alpha, and p53 proteins was found in 28.5%, 51.2%, 35.0%, and 29.3% of cases, respectively. TWIST expression was associated with higher histologic grade and unfavorable survival. TWIST expression was correlated with HIF1alpha expression and reduced E-cadherin expression. The altered HIF1alpha/TWIST/E-cadherin pathway was associated with lower overall survival (OS), while the co-expression of TWIST and p53 was correlated with lower progression-free survival. In the multivariate analyses, TWIST expression was an independent prognostic factor for OS.
CONCLUSIONS
Our data imply that TWIST expression could be a useful predictor of unfavorable prognosis for OEC. TWIST may affect the p53 tumor-suppressor pathway. Moreover, hypoxia-mediated EMT, which involves the HIF1alpha/TWIST/E-cadherin pathway may play an important role in the progression of OEC.

Keyword

Ovarian epithelial cancer; TWIST transcription factor; Cadherins; HIF1alpha; Tumor suppressor protein p53

MeSH Terms

Anoxia
Cadherins
Disease-Free Survival
Epithelial-Mesenchymal Transition
Immunohistochemistry
Multivariate Analysis
Prognosis
Tumor Suppressor Protein p53
Twist Transcription Factor
Cadherins
Tumor Suppressor Protein p53
Twist Transcription Factor