Analysis of microRNAs improves cytologic analysis of pancreatic fine-needle aspirates, allowing for more accurate identification of patients with pancreatic ductal adenocarcinoma (PDAC), researchers report in the October issue of Clinical Gastroenterology and Hepatology. This improvement could reduce the number of diagnostic procedures required for patients with pancreatic masses.
Endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA) and cytology analysis are used to diagnose and stage PDAC and other pancreatic lesions. However, its use in the clinic has been limited by high rates of indeterminate or false-negative results.
MicroRNAs are being tested as biomarkers for many cancers, including pancreatic cancer. They are stable and easily recovered from different types of clinical specimens, including fine-needle aspirates.
Randall E. Brand et al. aimed to develop and validate a microRNA-based test to improve detection of PDAC.
They used quantitative PCR to measure levels of 11 microRNAs in 95 formalin-fixed paraffin-embedded specimens (the standard) and 228 samples collected by EUS-FNA and from patients with solid pancreatic masses.
In EUS-FNA samples, this 5-microRNA classifier correctly identified 82.6% of PDACs and 96.1% of benign lesions, with an area under the curve value of 0.936. In the same specimens, cytopathology analysis correctly identified 78.8% of PDACs and 69.2% of benign lesions.
When cytology and microRNA analyses were combined, the tests accurately identified 90.8% of PDACs and 96.1% of benign lesions.
Furthermore, analysis of these microRNAs identified 22 additional cases of PDAC among 39 samples initially classified as benign, indeterminate, or nondiagnostic by cytology.
The authors propose using the microRNA analysis to identify PDAC in EUS-FNAs with a cytologic diagnosis other than adenocarcinoma or other malignancies.
Interestingly, 46 FNAs were collected without EUS guidance (percutaneously). An initial evaluation of these specimens with the 5-microRNA classifier showed a higher rate of technical failure (6.5%) and lower diagnostic sensitivity (58.3%). However, specificity and predictive value remained high (89.5% and 87.5%, respectively), whereas the performance of cytopathology was compromised significantly (lower rate of PDAC detection and higher nondiagnostic rate).
Brand et al. state that microRNA analysis could therefore help overcome some of the challenges of percutaneous biopsy collection.
Further studies are needed to learn more about what these microRNAs regulate (their targets) in pancreatic cells and why their levels correspond with cancer development.
Levels of MIR196A increase progressively with the grade of pancreatic intraepithelial neoplasm (PanIN), peaking at the stages of PanIN-2 and -3. Levels of MIR196A compared to those of MIR217, and levels of MIR135B compared to those of MIR24, have been previously used to distinguish PDAC from chronic pancreatitis. MIR148A and MIR130B have been shown to be down-regulated in pancreatic cancer.
Brand et al propose studies might also determine whether miRNAs can be used in determining prognosis and guiding therapy.