Transforming growth factor β receptors in verrucous and squamous cell carcinoma

Objectives: To study the intracellular location of transforming growth factor beta type II receptors (T beta R-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 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 expression was compared with expression of the type I receptor (T beta R-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. Interventions: None. Results: While in all VCs T beta R-II was found to be located along the membrane of the neoplastic keratinocytes, T beta R-II expression in SqCC was observed predominantly in a cytoplasmic location. This cytoplasmic location of T beta R-II was also seen in areas of transition from VC to SqCC. Expression 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 receptor to the growth inhibitory control of TGF-beta and may explain why VC tumors are less aggressive clinically. The marked reduction of membranous T beta R-II and their predominant cytoplasmic location diminishes TGF-beta growth inhibition and may contribute to the transformation of VC into the more aggressive SqCC.