RT Journal Article
SR Electronic
T1 Molecular heterogeneity of pancreatic intraductal papillary mucinous neoplasms and implications for novel endoscopic tissue sampling strategies
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 681
OP 686
DO 10.1136/jclinpath-2021-207598
VO 75
IS 10
A1 Rift, Charlotte Vestrup
A1 Melchior, Linea Cecilie
A1 Scheie, David
A1 Hansen, Carsten Palnæs
A1 Lund, Eva Løbner
A1 Hasselby, Jane Preuss
YR 2022
UL http://jcp.bmj.com/content/75/10/681.abstract
AB 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.Data are available upon reasonable request.