The prognostic significance of allelic imbalance at key chromosomal loci in oral cancer

Forty-eight primary oral squamous cell carcinomas (SCC) were screened for a llelic imbalance (Al) at 3p24-26, 3p21, 3p13, 8p21-23, 9p21, 9q22 and withi n the Rb, p53 and DCC tumour suppressor genes. Al was detected at ail TNM s tages with stage 4 tumours showing significantly more aberrations than stag e 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). Al at one or more loci within the 3p24-26, 3p21, 3p13 and 9p21 regions or within the THRB and DCC genes was a ssociated with reduced survival. The hazard ratios for survival analysis re vealed that patients with Al at 3p24-26, 3p13 and 9p21 have an approximatel y 25 times increase in their mortality rate relative to a patient retaining heterozygosity at these loci. Al at specific pairs of loci, D3S686 and D9S 171 and involving at least two of D3S1296, DCC and D9S43, was a better pred ictor 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 e ach tumour.