TP53 AND RAS MUTATIONS IN METACHRONOUS TUMORS FROM PATIENTS WITH CANCER OF THE UPPER AERODIGESTIVE TRACT

Patients who initially develop an upper aerodigestive tract cancer hav e an increased risk of second primary cancers. We examined TP53 and RA S mutations and p53 protein in 21 tumors from 10 patients with upper a erodigestive tract cancer who developed a metachronous tumor, to asses s the genetic changes that occur in multiple primary tumors from the s ame individual. Thirteen of 21 (62%) tumors were found to have mis-sen se mutations of either TP53 or RAS. Six tumors had TP53 mutations in c odons 5 to 8 and 10 tumors from 7 patients had mutations of codons 12 or 13 of K-RAS. Only one patient had concordance of a mutation in 2 tu mors; this mutation occurred in K-RAS and was accompanied by discordan ce of TP53 mutation. Three patients had tumors discordant for both TP5 3 and RAS mutations. Smoking-related tumors had TP53 and RAS mutations which were transversions in 11 (9 G:C to T:A and 2 G:C to C:G) and tr ansitions in 3 (2 G:C to A:T and 1 A:T to G:C). Tumors not associated with smoking contained only transitions (both G:C to A:T). p53 protein was detected by immunohistochemistry in 7 of 13 (54%) tumors and was concordant in the multiple tumors of 3 patients. Three of the 7 tumors staining for p53 also had TP53 mutations. Thus, genetic alterations a re discordant in multiple primary cancers and the pattern of mutations is similar to that found in patients with a single primary tumor, sup porting the concept that these cancers arise independently. (C) 1995 W iley-Liss, Inc.