Differential Expression of ras Signal Transduction Mediators in Verrucous and Squamous Cell Carcinomas of the Upper Aerodigestive Tract

Context.—ras gene mutations and expression of its gene product have been described in verrucous and squamous cell carcinomas. Other downstream signal-transduction mediators, extracellular signal-regulated kinases 1 and 2 (ERK-1 and ERK-2) and Raf-1, have not yet been as extensively studied. Objective.—To determine patterns of expression of ERK-1, ERK-2, and Raf-1 in verrucous and squamous cell carcinomas of the upper aerodigestive tract. Design.—Seventeen verrucous carcinomas and 10 squamous cell carcinomas of the upper aerodigestive tract were examined for the immunohistochemical expression of ERK-1, ERK-2, and Raf-1 product. Results.—Raf-1 expression was intensely expressed in the most basal portions of the epithelium in verrucous carcinomas, but was minimally expressed in the suprabasalar areas. Anti-Raf-1 staining of the squamous cell carcinomas was diffuse and patchy throughout the tumor cells and was weak in intensity. There was no geographic preference of staining. The cytoplasmic expression of both ERK-1 and ERK-2 was predominantly negative in the most basal layers of the epithelium in the verrucous carcinomas, but was positive in the suprabasalar region of the epithelium. Immunohistochemical expression of ERK-1 and ERK-2 in the squamous carcinomas was diffuse throughout the tumor. Conclusion.—There is strong correlation of the geographic expression of these mediators of ras signal transduction in verrucous and squamous carcinomas, but the cause of these differences remains unclear at present. The expression of these mediator proteins may have potential for diagnosis, as well as in understanding the biologic behavior of these lesions.