The prognostic significance of allelic imbalance at key chromosomal loci in oral cancer.
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.
Partridge
M
M
Kings College School of Medicine and Dentistry, Denmark Hill, London, UK.
Emilion
G
G
Pateromichelakis
S
S
A'Hern
R
R
Lee
G
G
Phillips
E
E
Langdon
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D016896:Treatment Outcome