Decreased Expression Levels of pfn1, tmsb4x and krt13 in Advanced Stage Oral Squamous Cell Carcinoma. Is There an Association with Disease Progression?

Introduction: The genes for TMSB4X and PFN1 are both highly expressed in oral tissue, and the proteins are found at high levels in saliva and in tissue. They are both actin monomer binding proteins and are thought to play a role in cell motility, a crucial pathway in tumor progression, such as breast cancers. We hypothesized that these proteins will be differentially expressed in squamous cell carcinoma (SCC) compared to benign lesions. In addition we investigated the potential differential expression of these proteins between malignant tissue and adjacent normal appearing epithelium. Since these proteins are involved in disease progression, alteration of their genes may assist in development of future treatment strategies.  

Materials and Methods: Achieved oral squamous cell carcinoma tumors were used to examine the levels of three proteins, TMSB4X, PFN1 and KRT13. Clinical, demographic, and histopathologic data was collected for 40 oral cavity SCCs that were treated with primary surgical resection. RNA was used to investigate for differences between expression levels of these genes in tumors versus benign oral mucosal lesions. Immunostaining for TMSB4X, PFN1 and KRT13 was then used to evaluate for differences in malignant tissue versus adjacent normal appearing epithelium.

Results: RNA analysis revealed no overall change in levels of these genes in tumor versus non-malignant oral lesions. Immunohistochemical analysis revealed both proteins were highly expressed in normal appearing basal epithelium while expression was minimal in the upper layers of the epithelium. In oral squamous cell carcinomas, SCCs, expression varied; in advanced stage tumors, PFN1 levels were lower as were they in tumors with nodal involvement. TMSB4X also trended toward reduced expression in late stage tumors. KRT13, showed opposite expression pattern. It was enriched in suprabasal differentiated oral mucosa epithelial cells and reported to be lost early in the tumor formation process.

Conclusions: These results emphasize the remarkably consistent loss of KRT13 with oral SCC formation and highlight its value as a marker for oral SCC. They also suggest the importance of further evaluation of two highly expressed oral epithelial proteins, TMSB4x and PFN1 in late steps of the cancer progression.