Objectives: To study the intracellular location of transforming growth factor beta type II receptors (TbetaR-II) in verrucous carcinoma (VC) and squamous cell carcinoma (SqCC), and to evaluate their role in the biological behavior of both neoplasias.
Design: Ten VC and 10 well-differentiated SqCC specimens were analyzed by immunohistochemistry and in situ hybridization for the expression and intracellular location of TbetaR-II. Receptor expression was evaluated in areas of invasion and in areas of transformation of VC into SqCC. TbetaR-II expression was compared with expression of the type I receptor (TbetaR-I).
Subjects: Formalin-fixed, paraffin-embedded tissue sections from VCs and well-differentiated SqCCs, operated on at the H. L. Moffitt Cancer Center and Research Institute from May 1987 to January 1998, were selected for the study.
Results: While in all VCs TbetaR-II was found to be located along the membrane of the neoplastic keratinocytes, TbetaR-II expression in SqCC was observed predominantly in a cytoplasmic location. This cytoplasmic location of TbetaR-II was also seen in areas of transition from VC to SqCC. Expression of TbetaR-I was found in a cytoplasmic location in both tumor types.
Conclusions: The membranous location of TbetaR-II in VC exposes the receptor to the growth inhibitory control of TGF-beta and may explain why VC tumors are less aggressive clinically. The marked reduction of membranous TbetaR-II and their predominant cytoplasmic location diminishes TGF-beta growth inhibition and may contribute to the transformation of VC into the more aggressive SqCC.