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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

3818 - Prevalence of KRAS mutation subtypes and MSI status in Pancreatic Cancer.

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Patan Gultawatvichai

Citation

Annals of Oncology (2018) 29 (suppl_8): viii670-viii682. 10.1093/annonc/mdy304

Authors

P. Gultawatvichai1, I. Puthawala2, K. Tomaszewicz3, V.G. Bathini4, L. Hutchinson3

Author affiliations

  • 1 Hematology-oncology, University of Massachusetts Medical center UMass Memorial Medical Center, 016551655 - Worcester/US
  • 2 Internal Medicine, University of Massachusetts Medical center UMass Memorial Medical Center, 1655 - Worcester/US
  • 3 Pathology, University of Massachusetts Medical center UMass Memorial Medical Center, 01605 - Worcester/US
  • 4 Hematology-oncology, University of Massachusetts Medical center UMass Memorial Medical Center, 1655 - Worcester/US
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Resources

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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