High Twist Expression Research Articles

High Twist expression is involved in infiltrative endometrial cancer and affects patient survival

Epithelial-mesenchymal transition (EMT) is critical not only for morphogenesis during embryonic development but also the conversion of early-stage tumors into infiltrative phenotypes. The present study examines the expression of Twist, a highly conserved bHLH transcription factor that is known to promote EMT, and evaluated its prognostic significance in endometrial cancers. Tissue specimens from 70 patients with endometrial cancer who underwent primary surgery were immunohistochemically evaluated for Twist expression. A semiquantitative scoring system was developed based on the intensity and extent of cancer cells with Twist expression. Thirty-six patients (51%) exhibited high Twist expression and 34 (49%) had low expression. Most cases exhibited both cytoplasmic and nuclear staining mainly observed in cancer foci and, preferentially, at the margin but, in some cases, the stromal cells located adjacent to cancer foci as well. Among various clinical variables, high Twist expression was significantly associated with deep myometrial invasion (>1/2) (P = .012) and concurrent with decreased E-cadherin expression (P < .001), a hallmark of EMT. In univariate survival analyses, both myometrial invasion and Twist expression influenced overall survival, but Cox multivariate analyses revealed that only Twist was an independent predictor of patient survival (hazard ratio, 5.12; P = .023). Thus, our data implies that high Twist expression is a potential novel prognostic factor for disease survival of endometrial cancer. Furthermore, the present study implicates Twist as a potential therapeutic target for this tumor type.

Aberrant expression of the tyrosine kinase receptor EphA4 and the transcription factor twist in Sézary syndrome identified by gene expression analysis.

Sézary syndrome (Sz) is a malignancy of CD4+ memory skin-homing T cells and presents with erythroderma, lymphadenopathy, and peripheral blood involvement. To gain more insight into the molecular features of Sz, oligonucleotide array analysis was performed comparing gene expression patterns of CD4+ T cells from peripheral blood of patients with Sz with those of patients with erythroderma secondary to dermatitis and healthy controls. Using unsupervised hierarchical clustering gene, expression patterns of T cells from patients with Sz were classified separately from those of benign T cells. One hundred twenty-three genes were identified as significantly differentially expressed and had an average fold change exceeding 2. T cells from patients with Sz demonstrated decreased expression of the following hematopoietic malignancy-linked tumor suppressor genes: TGF-beta receptor II, Mxi1, Riz1, CREB-binding protein, BCL11a, STAT4, and Forkhead Box O1A. Moreover, the tyrosine kinase receptor EphA4 and the potentially oncogenic transcription factor Twist were highly and selectively expressed in T cells of patients with Sz. High expression of EphA4 and Twist was also observed in lesional skin biopsy specimens of a subset of patients with cutaneous T cell lymphomas related to Sz, whereas their expression was nearly undetectable in benign T cells or in skin lesions of patients with inflammatory dermatoses. Detection of EphA4 and Twist may be used in the molecular diagnosis of Sz and related cutaneous T-cell lymphomas. Furthermore, the membrane-bound EphA4 receptor may serve as a target for directed therapeutic intervention.