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Abstract
Aims Intraductal papillary mucinous neoplasms (IPMNs) may be precursor lesions of pancreatic cancer. The path towards malignancy is associated with mutations in tumour suppressor—and oncogenes that may serve as biomarkers during diagnostic investigation. A novel micro forceps has made it possible to obtain biopsies from the cyst wall for analysis by next generation sequencing (NGS), providing an opportunity for early detection and intervention. However, the impact of spatial tumour heterogeneity on the representability of the biopsies has not been determined. The primary aim is to characterise the impact of molecular heterogeneity of the luminal cyst wall on tissue sampling strategies with small biopsies.
Methods We performed NGS and immunohistochemical phenotyping on 18 resected IPMNs with varying degrees of dysplasia and for a subset, concomitant carcinoma, using a commercially available NGS-panel of 51 oncogenes. We simulated endoscopic biopsies by performing punch biopsies (PBs) of the cyst wall from resected specimens.
Results In total, 127 NGS analyses were performed. Concomitant KRAS and GNAS was a common feature of the IPMNs. Mutations in KRAS and GNAS were associated with low-grade dysplasia whereas alterations in TP53, SMAD4, CDKN2A and PIK3CA were associated with high-grade dysplasia and/or carcinoma. The mutational analysis of the PBs from the cyst wall was compared with the whole lesion. No difference was detected between PBs and whole lesions when the cumulated mutational profile in increasing order of randomly performed PBs was compared.
Conclusions Small IPMN biopsies from the cyst wall are adequate to yield a molecular diagnosis.
- pancreatic neoplasms
- pancreas
- pathology
- molecular
- diagnostic techniques and procedures
Data availability statement
Data are available upon reasonable request.
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Data availability statement
Data are available upon reasonable request.
Footnotes
Handling editor Runjan Chetty.
Twitter @CVRift
Contributors CVR contributed to conceptualisation, methodology, analysis of data, writing—original draft. LCM contributed to conceptualisation, data analysis, review and revision of manuscript. DS contributed to conceptualisation, methodology, interpretation of data, review and revision of paper. CPH contributed to conceptualisation, methodology, data curation, review and revision of paper. ELL contributed to conceptualisation, methodology, review and revision of paper. JPH contributed to conceptualisation, methodology, data curation, review and revision of paper. All authors read and reviewed the paper and approved the final version.
Funding The study received funding from Rigshospitalets Research Foundation, The Novo Nordisk Foundation, The Danish Cancer Society, The Danish Cancer Research Foundation, Neye Foundation, Aase & Ejnar Danielsens Foundation and Anita & Tage Therkelsens Foundation.
Disclaimer The funding sources had no role in conducting the study or preparing the manuscript.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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