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

BACKGROUND, Allelic losses of tumor suppressor genes, or the chromosomal re gions harboring them, in the DNA of tumor cells may become useful postopera tive prognostic indicators. The authors studied frequent loss of heterozygo sity (LOH) on chromosome 8p22 and its association with disease progression that occurred later in patients with breast carcinoma. METHODS. To examine whether allelic losses at 8p22 might correlate with pos toperative survival during a 5-year period of prospective follow-up, the au thors tested tumors from a cohort of 298 breast carcinoma patients informat ive for 8p22 markers. The tumors were tested for allelic losses of microsat ellite markers D8S136 and D8S1106 located at 8p22, a chromosomal region whe re genetic alterations are frequent in breast carcinomas. RESULTS. Among the 298 breast carcinoma patients, 154 (52%) lost alleles in tumors. Patients whose tumors had lost an allele at 8p22 had a significant ly higher risk of postoperative mortality than those whose tumors retained both alleles at those loci; their 5-year mortality rates were 18% (26 patie nts died among 154 with losses at 8p22) versus 7% (10 patients died among 1 44 with retentions at 8p22) (P = 0.017). The 8p22 LOH was a significant ind ependent prognostic factor for postoperative survival in a group of patient s with large rumors (> 2.1 cm) and in a group of patients with estrogen rec eptor negative tumors in both univariate and multivariate analyses. These d ata show that 8p22 LOH was a significant prognostic factor for the postoper ative survival of certain clinical groups of patients who underwent surgery for breast carcinoma. CONCLUSIONS. Allelic loss on chromosome 8p22 can serve as a negative progno stic indicator to guide the postoperative management of patients, especiall y patients with large tumors (> 2.1 cm) and those with estrogen receptor ne gative tumors. Cancer 2000;88:1410-6. (C) 2000 American Cancer Society.