Abstract 3818
Background
KRAS is the most prevalent driver mutation in pancreatic ductal adenocarcinoma (PDAC) which impacts cell differentiation, proliferation, migration and apoptosis. KRAS subtypes may have prognostic significance but this finding remains uncertain. Microsatellite Instability / mismatch repair deficiency (MMR) has also been reported in PDAC but at a low frequency (0.8%) and these patients are eligible for immunotherapy. This study investigates the effect of KRAS subtype on survival rate and the prevalence of mismatch repair deficiency in our patient cohort.
Methods
91 patients enrolled from 2005 to 2012 with biopsy proven PDAC of all stages. All clinical data were collected from the medical records of each patient. Next generation sequencing was performed on all 91 samples. We also evaluated MMR expression in all resection specimens who underwent adjuvant treatment. Statistical analysis: Data were summarized as descriptive analysis statistics and analyzed using unpaired t-test. Overall survival (OS) was measured from the date of diagnosis to last known follow up or date of dead from disease.
Results
The most common type of mutation in all stages is KRAS (95%). KRAS mutation subtypes in the order of frequency were: G12D, G12V, G12R, Q61H, Q61L and G12C. Among codon 12 mutations, G12V showed the best OS at 20.12 months. Mutations in codon 61 carry better OS compared to codon 12 by 24 months (P = 0.0002, 95% CI 11.85 to 37.03). The staining for MMR status was performed on 30 of 91 specimens and all were mismatch repair protein proficient (analogous to MSI-stable [MSS]).
Conclusions
The prevalence and distribution of KRAS mutations from our study is similar to previous reports. Patients with a KRAS codon 61 mutation had better OS than with a codon 12 mutation. Interestingly, Q61 variants are far less common than the G12 variants which may explain why most of the pancreatic patients have an aggressive disease course. Our results support the conclusion that MMR defects are uncommon in PDAC. Germline mutation analysis could be considered to find other targetable mutations found in hereditary cancer syndromes such as BRCA1/2 or PALB2.
Clinical trial identification
Legal entity responsible for the study
Lloyd Hutchinson.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
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