Transforming growth factor beta receptors in verrucous and squamous cell carcinoma

Objectives: To study the intracellular location of transforming growth fact or beta type II receptors (T beta R-II) in verrucous carcinoma (VC) and squ amous cell carcinoma (SqCC), and to evaluate their role in the biological b ehavior of both neoplasias. Design: Ten VC and 10 well-differentiated SqCC specimens were analyzed by i mmunohistochemistry and in situ hybridization for the expression and intrac ellular location of T beta R-II. Receptor expression was evaluated in areas of invasion and in areas of transformation of VC into SqCC. T beta R-II ex pression was compared with expression of the type I receptor (T beta R-I). Subjects: Formalin-fixed, paraffin-embedded tissue sections from VCs and we ll-differentiated SqCCs, operated on at the H. L. Moffitt Cancer Center and Research Institute from May 1987 to January 1998, were selected for the st udy. Interventions: None. Results: While in all VCs T beta R-II was found to be located along the mem brane of the neoplastic keratinocytes, T beta R-II expression in SqCC was o bserved predominantly in a cytoplasmic location. This cytoplasmic location of T beta R-II was also seen in areas of transition from VC to SqCC. Expres sion of T beta R-I was found in a cytoplasmic location in both tumor types. Conclusions: The membranous location of T beta R-II in VC exposes the recep tor to the growth inhibitory control of TGF-beta and may explain why VC tum ors are less aggressive clinically. The marked reduction of membranous T be ta R-II and their predominant cytoplasmic location diminishes TGF-beta grow th inhibition and may contribute to the transformation of VC into the more aggressive SqCC.