THE LOSS OF HETEROZYGOSITY IN RETINOBLASTOMA AND P53 SUPPRESSOR GENESAS A PROGNOSTIC INDICATOR FOR HEAD AND NECK-CANCER

Inactivation of tumor suppressor genes, including p53 and retinoblasto ma (Rb), are commonly found in all cancers, including head and neck sq uamous cell carcinoma. Alterations at either p53 or Rb, however, are o nly weakly associated with tumor aggressiveness. In many cancers loss of heterozygosity (LOH) at multiple loci is associated with decreased survival. The polymerase chain reaction and highly informative microsa tellite markers were used to compare DNA from matched sets of 63 head and neck squamous cell cancers and normal tissue for LOH at the p53 an d Rb loci. At p53, 50 were informative, with LOH occurring in 19 (38%) , Of the 57 that were informative at Rb, LOH occurred in 21 (37%), Of the 46 that were informative at both p53 and Rb, LOH occurred in 10 (2 2%) at both loci, When LOH for p53 and Rb individually was compared to stage, differentiation, and survival, there was no correlation, Howev er, the patients with LOH at both loci had a significantly poorer surv ival (P = .009), This strongly supports the contention that simultaneo us alterations of these two tumor suppressor genes favor tumor aggress iveness and can be used as a prognostic indicator.