MICROSATELLITE INSTABILITY IS CORRELATED WITH LYMPH NODE-POSITIVE BREAST-CANCER

We analyzed 81 cases of primary breast carcinoma and 7 cases of fibroa denoma for microsatellite instability at eight loci, Twenty-seven case s (33.3%) manifested aberrant microsatellite alleles: 7 (8.6%) at one locus and 20 (24.7%) at two or more loci [tumors with replication erro r-positive (RER+) phenotype]. No evidence of microsatellite instabilit y was observed in fibroadenomas. We investigated correlations between RER+ phenotype and clinicopathological characteristics of the carcinom as, The RER+ phenotype was statistically associated with large tumor d iameter; of 19 RER+ tumors with measured size, 16 were >2 cm, compared to 28 of 58 tumors with no evidence of microsatellite instability or with shifts in allele sizes limited to one locus (P less than or equal to 0.005, chi(2) test). Consistently, there was also a strong statist ical association between RER+ phenotype and lymph node metastasis; 14 of 19 RER+ tumors with known lymph node status were N+, compared to 15 of 59 tumors with no evidence of microsatellite instability or with a llele shifts limited to one locus (P less than or equal to 0.0002, chi (2) test), Correlations with age of patients, proliferative activity, histotype (ductal versus lobular), and grade of differentiation were n ot statistically significant, although the RER+ phenotype was more fre quent in lobular and high-grade ductal carcinomas, in carcinomas with high proliferative activity, and in carcinomas from patients less than or equal to 50 years. Data concerning cancer(s) in first and/or secon d degree relatives were available for 66 cases, including 33 positive and 33 negative for family history of cancer, No correlations were det ected between RER+ phenotype and family history of cancer. In conclusi on, our results indicate that in breast cancer, microsatellite instabi lity is associated with clinicopathological parameters that are consid ered predictors of recurrent disease and aggressive behavior.