Abstracts
1997 Digestive Disease Week

Cancer of papilla of Vater: RER+ phenotype is associated with good prognosis.

A Scarpa*, C Iacono**, G Zamboni*, G Bogina*, L Bortolasi**, A Achille*, G Prati**, G Serio**. Departments of Pathology* and Surgery**, University of Verona, Verona, Italy.

Cancer of the papilla of Vater may be cured by surgery alone in up to 40% patients. There is general agreement that local spread of cancer is a reliable prognostic factor. Nevertheless, any cancer stage includes both long survivors and patients dying from their disease, indicating the need for additional factors capable of discerning prognosis among cancers at the same stage. During our studies aimed to clarify the molecular pathogenesis of cancers of the papilla of Vater, we noticed that genomic instability, of the type seen in replication error-phenotype (RER+) cancers, was associated with good outcome after pancreaticoduodenectomy. Therefore, we evaluated the possibility of using this genetic anomaly as a prognostic marker. Methods: We developed procedures to examine the presence of RER, using polymerase chain reaction and DNA from formalin-fixed paraffin-embedded tumors. RER status was assessed in 30 resected ampullary cancers. Of these, 11 patients had their disease still confined to the duodenal wall, whereas 19 had pancreatic and/or nodal involvement. Five of these patients (16%) had multiple synchronous or metachronous cancers in sites different from papilla of Vater. Results: Nine cancers (30%) showed a RER+ phenotype, including 6 cases confined to the duodenum and 3 advanced diseases. All these cases were consistently associated with long survival of patients (median 84 months, range 32-161), whereas patients with RER-negative cancers had a significantly poorer prognosis (median 14 months, range 4-31) (p = 0.001). A multivariate analysis including T stage, lymph node metastasis and tumor differentiation, RER status remained a strong predictive factor. In addition, 3 of 9 patients with RER+ cancers, but only 2 of 21 with RER-negative neoplasms were multiple cancer patients. Conclusion: Our data suggest that the use of molecular tests to identify RER+ phenotype cancers may serve to discern prognosis among cancers at the same stage. This might provide useful information in deciding whether add adjuvant therapy. We also report that the finding of a RER+ cancer may indicate a higher risk of multiple cancer development, mainly including gastric and colorectal sites.