Journal
JOURNAL OF CLINICAL PATHOLOGY
Volume 75, Issue 10, Pages 681-686Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/jclinpath-2021-207598
Keywords
pancreatic neoplasms; pancreas; pathology; molecular; diagnostic techniques and procedures
Categories
Funding
- Rigshospitalets Research Foundation
- Novo Nordisk Foundation
- Danish Cancer Society
- Danish Cancer Research Foundation
- Neye Foundation
- Aase & Ejnar Danielsens Foundation
- Anita & Tage Therkelsens Foundation
Ask authors/readers for more resources
The study aimed to investigate the impact of molecular heterogeneity of the luminal cyst wall on tissue sampling strategies for intraductal papillary mucinous neoplasms (IPMNs). NGS and immunohistochemical phenotyping on 18 IPMNs revealed various degrees of dysplasia and concomitant carcinoma. The results showed that small biopsies from the cyst wall are sufficient to provide a molecular diagnosis.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available