Evaluation of Brachyury Expression in Spindle Cell Carcinoma

Abstract

Epithelial-mesenchymal transition (EMT) is a complex biologic process by which epithelial cells lose their cytomorphologic characteristics and assume the phenotype of mesenchymal cells. EMT is essential to normal human embryogenesis, and also occurs in wound healing, tissue repair and cancer progression. Acquisition of a mesenchymal phenotype via EMT enhances the migratory capacity of carcinoma cells, increasing their metastatic capability and worsening prognosis for patients. One emerging marker of EMT is brachyury, a T-box transcription factor protein. Recent studies have demonstrated upregulation of brachyury in several carcinoma types, including squamous cell carcinoma (SCC). Spindle cell carcinoma (SpCC) is a variant of SCC in which cancer cells have a predominantly spindled phenotype. Whether brachyury is expressed in SpCC and contributes to this phenotypic change is not clear. We aimed to examine brachyury expression by immunohistochemistry in SpCC of the head and neck, hypothesizing that brachyury expression is increased in SpCC, as compared with other forms of SCC.

Immunohistochemical staining for brachyury was performed on 20 head and neck carcinoma cases per group in each of the following four groups: SpCC; moderately- to well-differentiated SCC; moderately- to poorly-differentiated SCC; and verrucous carcinoma (VC). Uninflamed fibroma was the negative control; and human chordoma, along with a 14.5-day-old mouse embryo, were positive controls. Evaluation of brachyury reactivity was completed by light microscopy. Brachyury expression was not seen in any of the experimental groups. Brachyury did not appear to be involved in the cytomorphologic changes present in SpCC, nor was it expressed in any head and neck SCC variants. Our results are contrary to those found in previous reports. This result suggests that an alternate mechanism contributes to the phenotype of SpCC.