MICROSATELLITE INSTABILITY IS ASSOCIATED WITH THE HISTOLOGICAL FEATURES OF THE TUMOR IN NONFAMILIAL COLORECTAL-CANCER

Replication errors (RERs) at microsatellite loci were examined in 46 s pecimens of nonfamilial colorectal cancer. Somatic microsatellite alte rations in at least two genetic loci, D11S904, D13S175, D2S123, and D1 0S197, consistent with a RER(+) phenotype were found in four cases (8. 7%). Six additional cases (138) showed alterations at a single locus. Mucinous differentiation was observed in 3 of 4 (75%) adenocarcinomas dth a RER(+) phenotype and only in 19% (8 of 42) of RER(-) adenocarcin omas (P < 0.05). A distinct cap of inflammatory cells at the advancing edge of the tumor and Crohn's-like reaction in peritumoral stroma wer e histologically identified in 50 and 25% of RER(+) and in 5 and 0% of RER(-) tumors, respectively (P < 0.05). Also, the plexiform pattern o f growth of carcinoma turned ant to be significantly associated with t he RER(+) phenotype (P < 0.05). Mucinous differentiation and stromal i nflammatory reactions are frequent features of hereditary nonpolyposis colorectal cancer in which germ-line mutations of mismatch repair gen es cause genetic instability. Our results indicate that a link exists between such histological features and somatic genetic instability con sistent with a RER(+) phenotype also in nonfamilial colorectal cancer.