Allelic loss at the 8p22 region as a prognostic factor in large and estrogen receptor negative breast carcinomas

Abstract

Allelic losses of tumor suppressor genes, or the chromosomal regions harboring them, in the DNA of tumor cells may become useful postoperative prognostic indicators. The authors studied frequent loss of heterozygosity (LOH) on chromosome 8p22 and its association with disease progression that occurred later in patients with breast carcinoma. To examine whether allelic losses at 8p22 might correlate with postoperative survival during a 5-year period of prospective follow-up, the authors tested tumors from a cohort of 298 breast carcinoma patients informative for 8p22 markers. The tumors were tested for allelic losses of microsatellite markers D8S136 and D8S1106 located at 8p22, a chromosomal region where genetic alterations are frequent in breast carcinomas. Among the 298 breast carcinoma patients, 154 (52%) lost alleles in tumors. Patients whose tumors had lost an allele at 8p22 had a significantly higher risk of postoperative mortality than those whose tumors retained both alleles at those loci; their 5-year mortality rates were 18% (26 patients died among 154 with losses at 8p22) versus 7% (10 patients died among 144 with retentions at 8p22) (P = 0.017). The 8p22 LOH was a significant independent prognostic factor for postoperative survival in a group of patients with large tumors (>2.1 cm) and in a group of patients with estrogen receptor negative tumors in both univariate and multivariate analyses. These data show that 8p22 LOH was a significant prognostic factor for the postoperative survival of certain clinical groups of patients who underwent surgery for breast carcinoma. Allelic loss on chromosome 8p22 can serve as a negative prognostic indicator to guide the postoperative management of patients, especially patients with large tumors (>2.1 cm) and those with estrogen receptor negative tumors.