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Microsatellite studies of oral cancer and premalignant lesions Poh, Catherine Fang-Yeu

Abstract

Oral squamous cell carcinoma (SCC) is believed to progress through sequential stages of premalignancies to invasive cancer. Once SCC is formed, the prognosis is poor. The 5-year survival rate of less than 50% is one of the worst among major human cancers. One of the essential keys to improving this gloomy prognosis lies in early diagnosis and proper management of premalignant lesions. A central dogma of carcinogenesis is that alteration to critical control genes underlies malignant transformation. A major focus of this thesis was to study early molecular pathways of oral cancer development and their impact on treatment. Loss of heterozygosity (LOH) has been shown to be a powerful molecular approach to detect genetic alteration of tumor suppressor genes in many organs and systems, including oral cancer and premalignant lesions. It is also the major molecular technique used in this thesis. Genetic changes in oral premalignant lesions and SCC studied (n=226) were investigated by microsatellite analysis for LOH at 19 loci on chromosome arms (3p, 9p, 17p, 4q, 8p, 11q, and 13q). This thesis has provided data to establish molecular progression models for both SCC and VC, which provide information on molecular cancer risk of premalignancies, and has yielded the first evidence that premalignancies with different molecular risks could be managed differently. It has also shown a possible role of HPV in the development of post-transplant oral SCC. These results not only provide insight into the mechanism of early cancer development but also suggest the use of these molecular assays as tools for targeting high-risk premalignancies. Hence, the studies have important clinical implications. The importance of the data is illustrated by the fact that a recent editorial on latest advances on genetic studies of oral premalignancies from the New England Journal of Medicine (Lippman and Hong, 2001) has cited 8 significant studies and one of these is from this thesis, and another from this lab with data from this thesis.

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