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Poster display session

2192 - The mutational landscape of periampullary adenocarcinomas in relation to morphological subtype and patient survival

Date

09 Sep 2017

Session

Poster display session

Topics

Translational Research;  Gastrointestinal Cancers

Presenters

Sebastian Lundgren

Citation

Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369

Authors

S. Lundgren1, E. Karnevi1, J. Elebro1, B. Nodin1, J. Eberhard1, K. Leandersson2, G.B. Jönsson1, K. Jirström1

Author affiliations

  • 1 Department Of Clinical Sciences, Lund University, 22185 - Lund/SE
  • 2 Cancer Immunology, Department Of Translational Medicine, Lund University, Malmö, Sweden, Lund University, 22185 - Lund/SE
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Resources

Abstract 2192

Background

Periampullary adenocarcinomas, including pancreatic cancer, are a heterogenous group of tumours. Despite improvements in oncological treatments in recent years, these patients still suffer from a poor prognosis. Emerging evidence shows that tumour morphology, intestinal type (I-type) and pancreatobililary type (PB-type), is a more relevant prognostic factor than anatomical tumour origin. The aim of this study was to map the mutational landscape in periampullary adenocarcinomas with particular reference to tumour morphology and prognosis.

Methods

The mutational status of 70 selected genes was mapped using next generation sequencing (NGS) in primary tumours from 103 patients with periampullary adenocarcinoma from a well-characterised consecutive cohort treated with pancreaticoduodenectomy at the University hospitals in Lund and Malmö, Sweden. Microsatellite instability (MSI) status was assessed by immunohistochemistry.

Results

The 5 most common mutations were TP53 (n = 55, 54.5%) followed by KRAS (n = 27, 46.5%), NF1 (n = 45, 44.6%), MAP3K1 (n = 40, 39,6%) and FGR1 (n = 22, 21.8%). Morphology or MSI status did not impact the burden of mutations. High tumour burden was not associated with patient survival. In the whole cohort, 9 mutations were prognostic (CDH1, CTNNB1, ERBB3, ERBB4, FGFR1, H6PD, KRAS, SH3BP4 and STK11). In I-type tumours, 6 mutations were prognostic (CDH1, CTNNB1, GATA3, KRAS, MYC and SH3BP4) while 5 mutations were prognostic in PB-type tumours (ERBB4, H6PD, NRAS, PARP1 and STK11). Notably, PARP1 and ERBB3 mutations were associated with improved prognosis. Adjusting for clinical parameters, two mutations remained significant in PB-type tumorus; STK11 (HR = 6.25; 95% CI 1.12-35.04) and PARP1 (HR = 0.86; 95% CI 0.10-0.71). In I-type tumorus, three mutations remained significant; KRAS (HR = 4.78; 95% CI 1.33-17.15), GATA3 (HR = 15.65; 95% CI 2.72-90.26) and CTNNB1 (HR = 9.03; 95% CI 1.18-69.05).

Conclusions

The results from this study demonstrate that the prognostic impact of different mutations, e.g. KRAS, in periampullary adenocarcinoma differs by morphological subtype. Thus, morphology is an important factor to consider in the development of novel targeted therapies and in biomarker studies.

Clinical trial identification

Legal entity responsible for the study

Lund University

Funding

Swedish Cancer Society, Swedish Research Council, Mrs Berta Kamprad Foundation

Disclosure

All authors have declared no conflicts of interest.

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