Survival in ampullary cancer: potential role of different KRAS mutations.

OBJECTIVE: The prognosis of ampullary adenocarcinoma (AA) usually is favorable; however, a subset of AA have poor biology and outcomes similar to pancreatic cancer. Patients in this subset will have early recurrence and death usually within 2 years. To date, there are no genetic markers to identify these patients. This study identifies the high-risk subset of AA and evaluates the mutational status of KRAS in predicting poor outcome.

METHODS: The tumor registry of an academic center was reviewed for data on patients managed operatively with AA. KRAS genotypes were determined for these patients using a polymerase chain reaction-based assay on clinical specimens. Analysis of variance and χ(2) tests was used to categorize continuous and categorical variables. Univariate and multivariate survival analyses were performed using Kaplan-Meier and Cox methods, respectively.

RESULTS: A total of 146 patients were identified with AA between 1982 and 2008. After stringent pathologic review, 97 patients were confirmed with AA, of whom 75 had tissue specimens available for analysis. Genotyping revealed 67% were wild-type (KRAS(WT)), and 33% were mutant for KRAS. Patients with KRAS(G12D) (n = 9), the most common mutational genotype, had poorer median survival (62 months) compared with those with KRAS(non-G12D) mutants (median survival not reached, mean 145 months) and KRAS(WT) patients (155 months, P = .05). Patients with survival ≤30 months were labeled "high-risk." Of the 9 patients with KRAS(G12D), 56% were in this high-risk subset, compared with 18% of KRAS(WT) (P = .02) and 31% of KRAS(non-G12D) (P > .05) populations. Patients with KRAS(G12D) also were more likely to present with advanced T stage.

CONCLUSION: The KRAS(G12D) mutation identifies a subset of AA patients with poor prognoses and may be used to identify patients at risk of early recurrence and poorer survival who may benefit from adjuvant therapy.