PROGNOSTIC VALUE OF DNA-PLOIDY AND C-ERBB-2 ONCOPROTEIN OVEREXPRESSION IN ADENOCARCINOMA OF BARRETTS-ESOPHAGUS

Background. During the last two decades, a rising incidence of adenoca rcinoma of the esophagus has been observed in the Western world. The p rognostic relevance of tumor-biological factors, such as DNA ploidy or c-erbB-2 overexpression, for overall survival following complete rese ction is still unknown. Methods. In a retrospective study of 80 patien ts with adenocarcinoma of Barrett's esophagus, the prognostic signific ance of flow cytometric DNA ploidy determination was investigated. Ove rexpression of c-erbB-2 oncoprotein was studied by immunohistochemical alkaline phosphatase-antialkaline phosphatase staining of formalin fi xed, paraffin embedded tissue sections of the primary tumor. Results. The rate of aneuploidy was 86%. Aneuploidy was significantly correlate d with lymph node metastases only. c-erbB-2 oncoprotein overexpression of the primary tumor was detected in 15 patients (19%). A significant correlation was seen between c-erbB-2 overexpression and depth of tum or invasion, lymph node involvement, distant metastases, and status of residual tumor after resection (R category, International Union Again st Cancer [UICC], 1987). All primary tumors with c-erbB-2 oncoprotein overexpression were aneuploid. In a multivariate Cox regression analys is for overall survival of those 62 patients (78%) whose tumor resecti on was macroscopically and microscopically complete (RO-UICC), depth o f invasion, distant metastases, and c-erbB-2 over-expression were inde pendent prognostic factors. The relative risk of death due to recurren ce was nearly identical for patients with either c-erbB-2 oncoprotein over-expression or distant metastases: 4.06 (1.4-11.8) and 3.94 (1.69. 5). In a multivariate Cox regression analysis of the subgroup of lymp h node-negative patients (n = 26), the ploidy status of the primary tu mor (defined as near-diploid plus tetraploid versus aneuploid plus mul tiploid) was the only independent prognostic factor for overall surviv al. Conclusions. These findings demonstrate that DNA ploidy as well as c-erbB-2 oncoprotein overexpression are valuable prognostic factors i n patients with adenocarcinoma of Barrett's esophagus after complete t umor resection.