CANCERS OF THE PAPILLA OF VATER - MUTATOR PHENOTYPE IS ASSOCIATED WITH GOOD PROGNOSIS

Cancer of the papilla (ampulla) of Vater is an uncommon disease that k ills 60% of affected patients, There is general agreement that local s pread of the tumor (T stage) is the only significant and independent p rognostic factor for this cancer, whereas the predictive value of tumo r grade and lymph node metastases is controversial, The genetic anomal ies involved in this process have the potential to serve as additional prognostic markers. We explored 25 ampullary cancers for the occurren ce of instability at simple repeat DNA sequences (microsatellites) of the type seen in replication error phenotype (PER-positive) cancers, T en microsatellites from five different chromosomes were amplified by P CR from both normal and cancer tissue DNA of the same patients, A tumo r was defined as PER-positive when microsatellite instability was foun d in the majority (greater than or equal to 6) of the loci analyzed. F ive cancers (20%) showed a RER phenotype and were associated with long survival of patients (32-96 months), whereas REP-negative cancers had a significantly poorer prognosis (Mantel-Cox test; P = 0.0084), with a median actuarial survival of 17 months. We also report that three (1 2%) patients belonged to cancer-prone families and four (16%) were can cer-prone individuals.