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Transforming Growth Factor Receptors in Verrucous and Squamous Cell Carcinoma

Meredith Anderson, BS; Carlos Muro-Cacho, MD, PhD; Joehassin Cordero, MD; Sandra Livingston, BS; Teresita Muñoz-Antonia, PhD

Arch Otolaryngol Head Neck Surg. 1999;125:849-854.

Objectives  To study the intracellular location of transforming growth factor type II receptors (TR-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 TR-II. Receptor expression was evaluated in areas of invasion and in areas of transformation of VC into SqCC. TR-II expression was compared with expression of the type I receptor (TR-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 TR-II was found to be located along the membrane of the neoplastic keratinocytes, TR-II expression in SqCC was observed predominantly in a cytoplasmic location. This cytoplasmic location of TR-II was also seen in areas of transition from VC to SqCC. Expression of TR-I was found in a cytoplasmic location in both tumor types.

Conclusions  The membranous location of TR-II in VC exposes the receptor to the growth inhibitory control of TGF- and may explain why VC tumors are less aggressive clinically. The marked reduction of membranous TR-II and their predominant cytoplasmic location diminishes TGF- growth inhibition and may contribute to the transformation of VC into the more aggressive SqCC.

From the Molecular Oncology Program (Ms Anderson and Dr Muñoz-Antonia) and Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute (Dr Muro-Cacho), Tampa, Fla; and the Departments of Pathology (Dr Muro-Cacho and Ms Livingston), Surgery (Dr Cordero), and Biochemistry and Molecular Biology (Dr Muñoz-Antonia), University of South Florida College of Medicine, Tampa.

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