TY - JOUR

T1 - Molecular heterogeneity of pancreatic intraductal papillary mucinous neoplasms and implications for novel endoscopic tissue sampling strategies

AU - Rift, Charlotte Vestrup

AU - Melchior, Linea Cecilie

AU - Scheie, David

AU - Hansen, Carsten Palnæs

AU - Lund, Eva Løbner

AU - Hasselby, Jane Preuss

N1 - Publisher Copyright: © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2022

Y1 - 2022

N2 - 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.

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.

KW - diagnostic techniques and procedures

KW - molecular

KW - pancreas

KW - pancreatic neoplasms

KW - pathology

U2 - 10.1136/jclinpath-2021-207598

DO - 10.1136/jclinpath-2021-207598

M3 - Journal article

C2 - 34039665

AN - SCOPUS:85106915332

VL - 75

SP - 681

EP - 686

JO - Journal of Clinical Pathology

JF - Journal of Clinical Pathology

SN - 0021-9746

IS - 10

ER -