Pathogenic alteration frequency by EUS FNA in malignant lymph node

Ferga C. Gleeson, MD, from the Division of Gastroenterology and Hepatology, Mayo Clinic, in Rochester, Minnesota, USA discusses this Original Article, “Frequency of mitogen-activated protein kinase and phosphoinositide 3-kinase signaling pathway pathogenic alterations in EUS-FNA sampled malignant lymph nodes in rectal cancer with theranostic potential.”

We have previously characterized EUS FNA cytology specimens by targeted next-generation sequencing (NGS) and demonstrated its possible role in precision medicine. Our focus was to determine the frequency and distribution of pathogenic alterations in malignant lymph node cytology specimens by the MAPK or PI3K signaling pathways in patients with sporadic, treatment naive, locally advanced primary rectal cancer with subsequent completed neoadjuvant therapy and on-site oncologic surgery. The MAPK and PI3K signaling pathways are core regulators of malignant transformation and tumor maintenance. Such pathway mutations are associated with sensitivity to certain chemotherapy agents to include MAPK inhibitors and PI3K-AKT-mechanistic target of rapamycin inhibitors. EUS has the potential to deliver cytologic and molecular diagnostic sub typing with predictive, prognostic and theranostic biomarkers.  The multi gene mutational landscape may reveal medically actionable pathogenic alterations to optimize anti-tumor therapy.

Multigene molecular profiling of  malignant lymph node cytology specimens targeted at least 2855 possible mutations within 50 cancer-associated genes and revealed 139 pathogenic alterations (2 [1-3] per patient) in 13 of 50 evaluated genes. The following represent a spectrum of identified alterations: TP53 (68%), APC (47%), KRAS (29%), FBXW7 (11%), NRAS (8%), PIK3CA (5%), SMAD4 (4%), and BRAF (4%). Pathogenic alterations were identified Pathogenic alterations were identified in the MAPK signaling pathway (KRAS, BRAF, NRAS, MEK), the PI3K signaling pathway (PIK3CA, AKT, STK11), and in 41% and 5%, respectively. No mutations were identified in the receptor tyrosine kinases gene family (MET, EGFR, ALK, KIT, PDGFRA, RET).

Figure 2. A, Scanned low magnification (10X) image of Pap-stained cytology slide showing areas of tumor selected for DNA extraction. B, Higher magnification (200X) of tumor cells from lymph node. C, Snapshot of amplicon reads showing a missense NRAS mutation. D, Snapshot of amplicon reads showing a missense FBXW7 mutation.

Targeted NGS of EUS FNA cytology specimens provides clinically relevant data that can help guide individualized therapy for oncology patients. The development of disease specific mini panels evaluating multi gene mutation profiles, copy number variants, and chromosomal rearrangements will further enhance our understanding of disease and aid the delivery of targeted therapy.

Read the abstract for this article online.

The information presented in Endoscopedia reflects the opinions of the authors and does not represent the position of the American Society for Gastrointestinal Endoscopy (ASGE). ASGE expressly disclaims any warranties or guarantees, expressed or implied, and is not liable for damages of any kind in connection with the material, information, or procedures set forth.

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