Chromosome 14q LOH in localized clear cell renal cell carcinoma.

The progression of a malignant tumour is understood to be the result of the accumulation of multiple genetic aberrations. As up to 14% of organ-confined renal cell carcinomas will recur after surgery, tumour clones with metastatic potential must already be present in some of these localized tumours. The association of 14q LOH with high-grade tumours and advanced tumour stage suggests an important role for the gene in tumour progression. Chromosome 14q LOH has been analysed in microdissected specimens from 130 organ-confined (UICC TNM stage 1 and 2) clear cell renal cell carcinomas using three microsatellite markers (D14S588, D14S617, GATA136B01). Tumours were classified as 14q LOH or not on the basis of LOH at one or more of the markers. The allelic imbalance ratio was used to determine both LOH and LOH proportion and the association between LOH and mortality, tumour size, histological grade and growth kinetics, measured by quantification of nucleolar organizer regions, was analysed. 14q LOH was present in 35.4% of informative cases at marker D14S588, 24.4% at D14S617, 36.4% at GATA136B01 and 39.5% for any one of the three markers. The mean 14q LOH proportion was 0.24 (range 0.009-0.80). LOH proportion correlated significantly with tumour size, AgNOR score and histological grade. It was also significantly associated with disease-specific mortality; (hazard ratio 1.22; 95% CI 1.02-1.45; p = 0.039). LOH proportion did not remain significant after adjusting for tumour size (hazard ratio 0.98; 95% CI 0.76-1.27; p = 0.90). These results indicate that the proportion of cells with 14q LOH in the tumour is associated with tumour aggressiveness; while this is not an independent predictor of survival, it may have some utility as a marker of latent metastatic potential.