Abstract CN14-04: Identifying the premalignant lesion at high risk for progression to cancer

Abstract

Abstract Oral tumorigenesis is a multistep process requiring the accumulation of multiple molecular alterations such as mutations, genomic deletions and amplifications, as well as epigenetic modifications in oral epithelial cells. These alterations allow the affected cells gaining growth advantages over other cells and other malignant phenotypes. In the past two decades, extensive studies have been conducted to understand molecular abnormalities in oral cancers and oral premalignant lesions (OPLs). Although promising, none of these has translated into a clinical test which can improve patient classification or cancer risk assessment. OPLs can exhibit a variety of histological features from hyperkeratosis, hyperplasia, and mild dysplasia to severe dysplasia. Together with other clinical features, our current practice has limited capability to accurately stratify cancer risk of patients with OPL. Such stratification is critical in our effort to develop surveillance measures for early cancer diagnosis and interventions to prevent or delay cancer development. In this presentation, I will focus on a series of biomarker discovery studies based on patients with OPL and enrolled in a prospective chemoprevention trial to illustrate some of the current efforts in oral cancer risk assessment based underlying molecular abnormalities in OPLs. The chemoprevention trial randomized 167 patients with biopsies obtained at the time of enrollment and certain time points during follow-up. One hundred and sixty-two patients had oral cancer-free survival data with the median time of follow-up about 7.5 years. During the follow-up period, 38 patients developed oral cancer but no statistically significant difference was observed in any of the treatment arms. We examined podoplanin expression, deltaNp63 expression, EGFR expression, EFGR copy numbers, global gene expression, and histopathologic features in OPLs from the patients obtained at either baseline or at 3 months follow-up. Potential roles of these factors in progression of OPLs and oral cancer risk were evaluated. Results suggest that these alterations may outperform previously reported biomarkers and clinicopathologic parameters in stratifying oral cancer risk of patients with OPLs. Development of oral cancer risk assessment strategies faces a number of challenges. Etiologies of OPLs and oral cancer may change over time, such as the emerging evidence of HPV infection in orapharyngeal cancers. Populations tested in many of our studies may be biased and not representative of the general population. Therefore, results may be difficult to validate in independent populations. We lack of systematic research networks at the national level to facilitate oral cancer risk assessment, early detection, and prevention. Efforts are lacking to integrate oral cancer risk assessment and chemoprevention programs. Some progresses and thoughts towards these limitations will be discussed. Citation Information: Cancer Prev Res 2010;3(12 Suppl):CN14-04.