Survival in ampullary cancer: Potential role of different KRAS mutations

• Published in: Surgery Vol. 157; no. 2; pp. 260 - 268
• Main Authors: Valsangkar, Nakul P., MD, Ingkakul, Thun, MD, Correa-Gallego, Camilo, MD, Mino-Kenudson, Mari, MD, Masia, Ricard, MD, PhD, Lillemoe, Keith D., MD, Castillo, Carlos Fernández-del, MD, Warshaw, Andrew L., MD, Liss, Andrew S., PhD, Thayer, Sarah P., MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2015
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Amino Acid Substitution; Ampulla of Vater; Biomarkers, Tumor - genetics; Common Bile Duct Neoplasms - genetics; Common Bile Duct Neoplasms - mortality; Common Bile Duct Neoplasms - pathology; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mutation; Point Mutation; Prognosis; Proportional Hazards Models; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; Retrospective Studies; Risk Factors; Surgery
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1016/j.surg.2014.08.092

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 χ2 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.