MICROSATELLITE INSTABILITY AND P53 MUTATIONS IN SPORADIC RIGHT AND LEFT COLON-CARCINOMA - DIFFERENT CLINICAL AND MOLECULAR IMPLICATIONS

BACKGROUND. Left and right colon carcinomas can display different clin ical, pathologic, and genetic characteristics. The purpose of this stu dy was to characterize multiple molecular genetic alterations in spora dic colon carcinoma and to correlate them with the location of the tum ors and with lymph node metastasis. METHODS. One hundred and twenty-fi ve cases of sporadic colon carcinoma (50 in the right colon and 75 in the left colon in patients with no family history of colon carcinoma) were studied. Status of the p53 gene was assessed by polymerase chain reaction (PCR), single strand conformation polymorphism, and sequencin g at exons 5-8. Microsatellite instability was analyzed with five micr osatellite markers at chromosome 18. The mismatch repair genes hMLH1 a nd hMSH2 were studied in tumors found to have microsatellite instabili ty by PCR and sequencing. RESULTS. In the 125 cases studied, there wer e 53 tumors with mutations of the p53 gene. p53 mutations correlated w ith lymph node metastases from right colon carcinoma cases (61%), and all cases with p53 mutations and microsatellite instability were AJCC/ UICC Stage III (Dukes Stage C). In the right colon carcinoma cases the rate of microsatellite instability was related to the tumor size (19% in tumors measuring < 4 cm, and 34% in tumors measuring > 4 cm). No c orrelation between microsatellite instability and p53 mutations was de tected. In the left colon carcinoma cases, p53 mutations were detected in 41% of tumors and microsatellite instability in 14%; neither findi ng was related to the tumor size. Mutations of the hMLH1 and hMSH2 mis match repair genes were detected in 7 of 24 cases with marked microsat ellite instability. CONCLUSIONS. Microsatellite instability is prone t o occur in sporadic right colon carcinoma during tumor growth and is n ot associated significantly with mutations in the hMLH1 and hMSH2 mism atch repair genes or in the p53 gene. Concomitant detection of microsa tellite instability and p53 mutations in right colon carcinoma is asso ciated with the presence of lymph node metastases. (C) 1998 American C ancer Society.