Comprehensive molecular profiling of pancreatic ductal adenocarcinoma in FNA, biopsy, and resection specimens

Abstract

BACKGROUND Molecular testing to identify molecular alterations in pancreatic ductal adenocarcinoma (PDAC) has been increasingly requested because of potential therapeutic implications. In this study, we compared the performance of PDAC fine‐needle aspiration (FNA), fine‐needle biopsy (FNB), and resection specimens for comprehensive molecular analysis. METHODS A next‐generation sequencing–based Oncomine Comprehensive Assay (OCA) was used to analyze molecular alterations in FNA, FNB, or resection specimens. We examined adequacy and success rates for completion of molecular testing and catalogued molecular alterations in these specimen types. RESULTS The cohort included 23 FNA, 20 FNB, and 27 resection cases. Gene mutation or amplification analysis was successful in 18 (78%) FNA and 16 (80%) FNB specimens, whereas gene fusion assessment succeeded in 12 (52%) FNA and 12 (60%) FNB samples. All 27 (100%) resection specimens were adequate for complete OCA. There were significant differences in success rates for mutation and amplification analysis between resection and FNA or FNB specimens (P < .01) but not between FNA and FNB samples (P > .05). Manual microdissection was less likely to be performed for FNA specimens than FNB or resection specimens (P < .01). KRAS mutation was the most common mutation identified (90%), followed by mutations in TP53 (64%), CDKN2A (25%), and SMAD4 (15%) genes. CONCLUSIONS Our study demonstrated similar success rates for comprehensive molecular analysis using FNA and FNB specimens of PDAC, suggesting that FNA material could serve as an alternative source for comprehensive molecular testing. The molecular alterations identified in these specimens may have potential diagnostic and therapeutic implications.;

Comprehensive Genomic Studies on the Cell Blocks of Pancreatic Cancer

“…In comparison to fine-needle biopsy (FNB) samples, studies have demonstrated similar success rates for comprehensive molecular analysis using FNA and FNB specimens of pancreatic adenocarcinoma, with complete concordance between the histologic sample and the corresponding cytologic material in almost 90% of cases [11,14]. In a study by Gan et al (2022) [15], CBs were presumed to represent samples obtained from EUS-FNB and yield optimal material for targeted NGS in PDACs, similar to cytological smears.…”

Improving diagnostic yield of pancreatic serous cystadenoma with cyst fluid ancillary testing, adjunct immunohistochemistry, and additional fine‐needle biopsy sampling

“…[26][27][28] KRAS mutation in cystic fluid have relatively high sensitivity and specificity for IPMNs, 29,30 which is also the most common mutation (90%) identified in pancreatic ductal adenocarcinoma. 31 However, a small portion of mucinous cysts can have a wild-type KRAS. Thus, the specimen with a negative KRAS mutation cannot reliably be classified as a nonmucinous cyst; a diagnosis of SCA based on a negative KRAS mutation would be far from reach.…”

“…Previous whole exome sequencing studies have identified a specific mutation profile for pancreatic cystic lesions including VHL in SCA, CTNNB1 in solid pseudopapillary neoplasm, and KRAS in MCN and IPMN 26–28 . KRAS mutation in cystic fluid have relatively high sensitivity and specificity for IPMNs, 29,30 which is also the most common mutation (90%) identified in pancreatic ductal adenocarcinoma 31 . However, a small portion of mucinous cysts can have a wild‐type KRAS .…”

Mutation Analysis of Pancreatic Juice and Plasma for the Detection of Pancreatic Cancer

“…Molecular profiling of tissue collected by fine-needle biopsy (FNB)-to assess these mutations-is less applicable for surveillance purposes, as it is invasive, relies on a visible mass, and is expected to obtain information from a single clone. Additionally, collection during endoscopic ultrasound (EUS) has been challenging due to low tumor cellularity and limited yield of tissue [4,5]. To date, for PC, carbohydrate antigen 19.9 (CA19.9) is the only serum marker implemented in clinical practice.…”