High overall copy number variation burden by genome-wide methylation profiling holds negative prognostic value in surgically treated pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of cancer with an overall 5-year survival of around 10 %. New prognostic tools to stratify patients are needed. Our main aim was to evaluate the prognostic value of overall copy number variation (CNV) burden in surgically treated PDAC. DNA extracted from 108 surgical PDAC specimens was examined to collect data on the genome-wide DNA methylation status of >850,000 CpG sites in promoter, gene body, and enhancer regions (Illumina Infinium Methylation EPIC BeadChip Kit). CNV profiles were obtained and all PDACs were stratified into one of three groups: Low, moderate, or high overall CNV burden. Tumors histologically showing a dominant conventional and/or tubulopapillary pattern in 60 %-100 % and 0-59 % were categorized as Group A and Group B as per Kalimuthu. We also performed targeted next-generation sequencing (NGS) and immunohistochemistry. High overall CNV burden held independent negative prognostic value with poor survival (HR 4.01 (95%CI 1.96-8.19), p = 0.00014) and was more frequent in Group B (p = 0.0003). Most frequent chromosomal arm-level aberrations were gains of 8q (29 %) and 1q (19 %) and losses of 17p (55 %), 18q (43 %), 6q (37 %), 9p (36 %), 6p (26 %), 19p (26 %), and 8p (25 %). Most frequent mutations found were in KRAS (95 %), TP53 (62 %), CDKN2A (24 %), SMAD4 (23 %), ATM (9 %), ARID1A (7 %), RNF43 (7 %), GNAS (6 %), and KDM6A (6 %). Group A PDACs showed more frequently KRAS variants other than Gly12Val and Gly12Asp (p = 0.012). Our data indicate that overall CNV burden using genome-wide methylation profiling may be a useful prognostic tool in surgically treated PDAC. Importantly, our approach, using data from genome-wide methylation profiling for analysis of overall CNV burden, can be performed on formalin-fixed and paraffin embedded PDAC tissues. Future studies should examine the prognostic value of overall CNV burden in unresectable PDAC.

Accuracy and clinical outcomes of pancreatic EUS-guided fine-needle biopsy in a consecutive series of 852 specimens.

Background and Objectives: Pancreatic EUS-guided fine needle biopsy (EUS-FNB) is increasingly used. Accuracy of EUS-FNB, particularly for benign diseases, utility of additional EUS-FNB if malignancy is suspected but initial diagnosis is inconclusive, and complication rate are not fully elucidated. We evaluated operating characteristics of EUS-FNB overall and for different diagnostic categories, value of additional EUS-FNB if malignancy is suspected but initial diagnosis is inconclusive, and frequency and type of complications. Methods: A retrospective tertiary single-center study including 852 consecutive pancreatic SharkCore EUS-FNBs from 723 patients between 2015 and 2020. EUS-FNB diagnoses were applied according to Papanicolaou Society's system and each category was further subcategorized. Results: Sufficient tissue cylinders for a histologic diagnosis were obtained in 93.4% (796/852). Accuracy was overall, for malignant, and benign entities 85.6% (confidence interval [CI]: 83.2%-87.9%), 88.3% (CI: 85.9%-90.4%), and 94% (CI: 92.2%-95.5%). Sensitivity and accuracy of EUS-FNB for autoimmune pancreatitis (AIP) (n = 15) was 83.3% (CI: 58.6%-96.4%) and 99.2% (CI: 98.3%-99.7%). Of patients in whom malignancy was suspected but initial EUS-FNB diagnosis was inconclusive, 7.3% (53/723) underwent one or two additional EUS-FNBs, and in 54.7% (29/53) of these, a malignant diagnosis was established. The frequency of hospitalization following EUS-FNB was 4.7%, with 0.2% (n = 2) incidents needing active intervention. Conclusions: We found a high accuracy of pancreatic EUS-FNB across all diagnostic categories including rare entities, such as AIP. In patients with a clinical suspicion of malignancy, additional EUS-FNB resulted in a conclusive diagnosis in more than half of cases. Complications necessitate hospitalization in almost 5%, but the majority are self-limiting.