Prognostic value of DNA ploidy and c-erbB-2 oncoprotein overexpression in adenocarcinoma of Barrett's esophagus.
BACKGROUND
During the last two decades, a rising incidence of adenocarcinoma of the esophagus has been observed in the Western world. The prognostic relevance of tumor-biological factors, such as DNA ploidy or c-erbB-2 overexpression, for overall survival following complete resection is still unknown.


METHODS
In a retrospective study of 80 patients with adenocarcinoma of Barrett's esophagus, the prognostic significance of flow cytometric DNA ploidy determination was investigated. Overexpression of c-erbB-2 oncoprotein was studied by immunohistochemical alkaline phosphatase-antialkaline phosphatase staining of formalin fixed, paraffin embedded tissue sections of the primary tumor.


RESULTS
The rate of aneuploidy was 86%. Aneuploidy was significantly correlated 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 tumor invasion, lymph node involvement, distant metastases, and status of residual tumor after resection (R category, International Union Against Cancer [UICC], 1987). All primary tumors with c-erbB-2 oncoprotein overexpression were aneuploid. In a multivariate Cox regression analysis for overall survival of those 62 patients (78%) whose tumor resection was macroscopically and microscopically complete (R0-UICC), depth of invasion, distant metastases, and c-erbB-2 overexpression were independent prognostic factors. The relative risk of death due to recurrence was nearly identical for patients with either c-erbB-2 oncoprotein overexpression or distant metastases: 4.06 (1.4-11.8) and 3.94 (1.6-9.5). In a multivariate Cox regression analysis of the subgroup of lymph node-negative patients (n = 26), the ploidy status of the primary tumor (defined as near-diploid plus tetraploid versus aneuploid plus multiploid) was the only independent prognostic factor for overall survival.


CONCLUSIONS
These findings demonstrate that DNA ploidy as well as c-erbB-2 oncoprotein overexpression are valuable prognostic factors in patients with adenocarcinoma of Barrett's esophagus after complete tumor resection.
Nakamura
T
T
Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Germany.
Nekarda
H
H
Hoelscher
A H
AH
Bollschweiler
E
E
Harbeck
N
N
Becker
K
K
Siewert
J R
JR
Harbec N [corrected to Harbeck
N ]
N]
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000782:Aneuploidy; D001471:Barrett Esophagus / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D004171:Diploidy; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016629:Esophagectomy; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011003:Ploidies; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases; D012189:Retrospective Studies; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D004247:DNA; D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases