Background and study aims Needle tract seeding during endoscopic ultrasound fine-needle biopsy (EUS-FNB) remains a concern. We investigated whether such seeding occurred in a patient with pancreatic ductal adenocarcinoma (PDA).
Patient and methods Surgically resected and EUS-FNB-derived specimens were genotyped to determine if a gastric wall tumor that emerged 3 years after curative resection of an early-stage PDA was clonally related to the original tumor.
Results The gastric tumor histologically resembled the primary PDA; the lesions also shared KRAS, SMAD4, and RNF43 mutations. Genotyping of the preoperative EUS-FNB specimen, in which cancer was not detected, nevertheless revealed mutations that were identical to those in the resected primary and recurrent tumors. While the primary PDA had a low frequency of mutant SMAD4, such mutations were highly prevalent in both the EUS-FNB and recurrent tumor specimens.
Conclusions The genetic lineages of sampled tissues from our patient revealed that needle tract seeding may have incidentally occurred when a subset of neoplastic cells within a heterogeneous tumor (i. e., an aggressive clone) was targeted during EUS-FNB.
Background Mutations in GNAS drive pancreatic tumorigenesis and frequently occur in intraductal papillary mucinous neoplasm (IPMN); however, their value as a therapeutic target is yet to be determined. This study aimed at evaluating the involvement of mutant GNAS in tumor aggressiveness in established pancreatic cancer. Methods CRISPR/Cas9-mediated GNAS R201H silencing was performed using human primary IPMN-associated pancreatic cancer cells. The role of oncogenic GNAS in tumor maintenance was evaluated by conducting cell culture and xenograft experiments, and western blotting and transcriptome analyses were performed to uncover GNAS-driven signatures. Results Xenografts of GNAS wild-type cells were characterized by a higher Ki-67 labeling index relative to GNASmutant cells. Phenotypic alterations in the GNAS wild-type tumors resulted in a significant reduction in mucin production accompanied by solid with massive stromal components. Transcriptional profiling suggested an apparent conflict of mutant GNAS with KRAS signaling. A significantly higher Notch intercellular domain (NICD) was observed in the nuclear fraction of GNAS wild-type cells. Meanwhile, inhibition of protein kinase A (PKA) induced NICD in GNAS-mutant IPMN cells, suggesting that NOTCH signaling is negatively regulated by the GNAS-PKA pathway. GNAS wild-type cells were characterized by a significant invasive property relative to GNAS-mutant cells, which was mediated through the NOTCH regulatory pathway. Conclusions Oncogenic GNAS induces mucin production, not only via MUC2 but also via MUC5AC/B, which may enlarge cystic lesions in the pancreas. The mutation may also limit tumor aggressiveness by attenuating NOTCH signaling; therefore, such tumor-suppressing effects must be considered when therapeutically inhibiting the GNAS pathway.
Background
Despite advances in the diagnosis of pancreatic ductal adenocarcinoma (PDA), histological evaluation of small and poorly defined masses in the pancreas is uncomfortable and unsafe.
Methods
We herein report a case of early stage PDA, in which multiple KRAS mutations were detected in the pancreatic juice preoperatively. A small hypoechoic area adjacent to the portal vein was detected through endoscopic ultrasound in the pancreatic body. KRAS mutations were evaluated using plasma, and the pancreatic juice by digital PCR.
Results
Pancreatic duct biopsy and pancreatic juice cytology were performed with no evidence of malignancy; however, KRAS mutations, KRAS G12V and G12D, were detected in the pancreatic juice. Histological assessment of the resected specimen demonstrated a solid tumor with desmoplastic reaction accompanied by carcinoma in situ in the main pancreatic duct where KRAS G12V mutation was identified. More detailed analysis demonstrated KRAS G12D mutation in the cluster of low grade pancreatic intraepithelial neoplasia, implying that the lesion developed independently.
Conclusions
Our study indicates the potential of “endoscopic liquid biopsy” to capture the driver gene for PDA diagnosis.
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