Abstract
Forty-eight primary oral squamous cell carcinomas (SCC) were screened for allelic imbalance (AI) at 3p24-26, 3p21, 3p13, 8p21-23, 9p21, 9q22 and within the Rb, p53 and DCC tumour suppressor genes. AI was detected at all TNM stages with stage 4 tumours showing significantly more aberrations than stage 1-3. A factional allelic loss (FAL) score was calculated for all tumours and a high score was associated with development of local recurrence (P = 0.033) and reduced survival (P = 0.0006). AI at one or more loci within the 3p24-26, 3p21, 3p13 and 9p21 regions or within the THRB and DCC genes was associated with reduced survival. The hazard ratios for survival analysis revealed that patients with AI at 3p24-26, 3p13 and 9p21 have an approximately 25 times increase in their mortality rate relative to a patient retaining heterozygosity at these loci. AI at specific pairs of loci, D3S686 and D9S171 and involving at least two of D3S1296, DCC and D9S43, was a better predictor of prognosis than the FAL score or TNM stage. These data suggest that it will be possible to develop a molecular staging system which will be a better predict of outcome than conventional clinicopathological features as the molecular events represent fundamental biological characteristics of each tumour.
Highlights
The TNM tumour classification system together with tumour site, type, grade and thickness, are all used to predict which patients are at risk of developing local or distant recurrence and plan adjuvant therapy (Spiro et al, 1986; Anneroth et al, 1987; Langdon and Henk 1995)
Despite taking into account all the available prognostic information when making crucial decisions about treatment, many patients develop local or distant recurrence. This failure is due to the inability to detect small numbers of malignant cells which remain in the body after treatment and the requirement to take into account information about tumour biology in addition to the conventional clinical and histologic prognostic criteria
In this study we have looked for allelic imbalance (AI) at 19 loci at chromosomes 3p, 8p21–23, 9p13–21, 9q22, 13q14.2 and within the p53, Rb and DCC tumour suppressor genes since these sequences have all been implicated in the pathogenesis of head and neck and oral squamous cell carcinomas (SCC)
Summary
The TNM tumour classification system together with tumour site, type, grade and thickness, are all used to predict which patients are at risk of developing local or distant recurrence and plan adjuvant therapy (Spiro et al, 1986; Anneroth et al, 1987; Langdon and Henk 1995). Despite taking into account all the available prognostic information when making crucial decisions about treatment, many patients develop local or distant recurrence. This failure is due to the inability to detect small numbers of malignant cells which remain in the body after treatment and the requirement to take into account information about tumour biology in addition to the conventional clinical and histologic prognostic criteria
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