AT1 angiotensin II receptor subtype in the human larynx and squamous laryngeal carcinoma

The presence of the angiotensin type 1 receptor (AT1 Ang II-R) was investigated in normal and diseased human larynx using a specific monoclonal antibody (6313/G2). When tissue AT1 content was studied by SDS electrophoresis with immunoblotting, the receptor was detected in 10/10 laryngeal tumours, and in 7/10 samples of normal tissue from the same patients. Two immunostaining bands, approximately 75 kDa, were present in all cases. Immunocytochemistry performed on sections of 45 formalin-fixed, paraffin-embedded laryngeal tissue samples showed that the receptor was expressed in normal respiratory epithelium only in a perinuclear pattern, above the nucleus toward the cell apex. In addition, the antigen was invariably present in skeletal muscle cells and in the columnar duct epithelium of minor salivary glands. The secretory cells were negative, but the antibody stained the adjacent myoepithelial cell layer. As expected, smooth muscle cells of the vessel walls also expressed Ang II-R. In metaplastic epithelium deriving from respiratory epithelium, the receptors were distributed diffusely throughout the cytoplasm of basal and parabasal cells. In dysplastic epithelium, cells of all layers were strongly positive. Finally, squamous cell tumours showed varying numbers of immunoreactive cells, which stained in a diffuse cytoplasmic and membranous pattern. Computer-assisted image analysis of the stained sections showed that the positivity for Ang II-R dramatically increased in dysplastic and well-differentiated cancer cells (3- and 5.5-fold higher than in normal epithelium, respectively), but there was less in poorly and very poorly differentiated cancer. Receptor abundance was not correlated with tumour size nor lymph node involvement. These results suggest a possible role of Ang II in the growth or function of normal and neoplastic larynx tissue, which is especially significant in early neoplastic change.