Clinicopathologic features of patients with KRAS wild-type pancreatic adenocarcinoma.

Abstract

192 Background: Pancreatic adenocarcinoma (PC) has the highest frequency of KRAS gene mutations among human cancers. A better understanding of disease biology may help improve targeted therapies for this disease. There is limited data about clinical, pathological features and treatment outcomes in patients (Pts) with wild type KRAS tumors (KRASwt). Methods: Retrospective review of 71 pts with histologically confirmed PC between 2009 and 2012 was undertaken. The KRAS codon 12 and 13 and BRAF codon 600 mutations were assessed in diagnostic tumor tissues (TrimGen Mutector II Shifted Termination Assay). Differences were evaluated with t-test and Fisher exact test. Results: KRAS mutations were identified in 50 tumors (70%), while 21 tumors (30%) had KRASwt genotype. Almost all (96%) mutations occurred at codon 12, there were no mutations in codon 13, and none of the KRASwt tumors harbored BRAF mutations. Pts with KRASwt tumors were mostly white (76%), females (57%), and did not have diabetes mellitus (80%). At diagnosis, pts with KRASwt tumors had a tendency to present at younger age (median age of 60 vs. 66 y; P = 0.1) and with lower CA19-9 values (median CA19-9: 392 vs. 3371 U/mL; P=0.042). Head of the pancreas was the primary site of disease in the majority of pts with KRAS wt tumors (58%), while body or tail was the primary site of disease in the majority of pts with KRAS mutant tumors (53%). There was no difference in the histologic differentiation. Although the majority of pts with KRAS wt (55%) and mutant tumors (57%) presented with distant metastases or locally advanced disease (40% and 39%; respectively), liver involvement was seen in only 55% of pts with KRAS wt tumors vs 92% in the pts with mutant tumors (p=0.016). In univariable analysis, age was an independent predictor of overall survival (HR 1.14, p=0.037) in pts with KRAS wt tumors, while level of bilirubin at presentation was a predictor of overall survival (HR 1.86 (0.77, 4.53); P <0.0001) in pts with KRAS wttumors who had distant metastasis. Conclusions: The frequency of pts with PC who had KRASwt tumors was higher than previously described. Pts with KRASwt tumors may have a disease that is biologically different than those with mutated KRAS. Further prospective characterization is warranted.