Abstract 1490: Role for Id1 in oral cancer progression

Abstract

Abstract This investigation determined whether Id1 expression in lesions or lesion associated vessels increases during the progression of oral cancer. Oral cancer incidence is increasing and there has been no change in the five year survival rate for the disease in several decades. Biomarkers to identify early lesions that are likely to progress to cancer and targets for therapy of later stage disease are urgently needed. This work extends a previous study linking Id1 (inhibitor of DNA binding/differentiation) with oral cancer by examining Id1 expression during oral cancer progression and its association with angiogenesis. If we can obtain evidence that expression of Id1 is elevated in dysplasias or their associated vessels and correlates with those dysplasias that progress to cancer, Id1 would be a potential biomarker for the disease and possibly a target for therapeutic intervention. Expression of Id1 and the endothelial marker CD31 were determined by immunohistochemistry in serial sections of human normal oral mucosa, dysplastic lesions, squamous cell carcinomas (SCC) that have not metastasised to date and those that have metastasised to lymph nodes. The Id1 antibody used has been shown to be highly specific for the protein in contrast to other Id1 antibodies that have been used in previous studies which have recently been shown to detect additional non-specific proteins. The proportion of vessels positive for Id1 was determined by Chalkley counting, a method suggested to be used as a standard in an international consensus on quantification of angiogenesis. In all sections, 5 areas with a high density of vessels were selected and Chalkley counts performed to determine the number of vessels as detected by CD31 expression and the proportion of those that were positive for Id1. Our results show that there is a marked increase in Id1 intensity and the proportion of cells that are positive for Id1 in lesions (dysplasia, SCC that that had metastasised and those that to date have not) as compared to normal oral mucosa. More samples are needed, however, to confirm whether Id1 could be used as a biomarker for oral cancer. In tumour vasculature, both the intensity of Id1 expression and the percent of endothelial cells positive for the protein correlated with tumour aggressiveness, with the highest expression levels evident in the SCCs that have metastasised to lymph nodes. These data suggest that Id1 might be a good target for therapy of SCC and that Id1 may play a role in neoangiogenesis in oral cancer. In conclusion our data demonstrate that Id1 expression could be a biomarker for oral SCC, correlates with tumour aggressiveness and may play a role in neoangiogenesis in the disease. As the main site to which oral SCCs metastasise are the lymph nodes, we aim to extend this work to determine whether Id1 may be responsible for neolymphangiogenesis in this disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1490. doi:10.1158/1538-7445.AM2011-1490