Abstract | BACKGROUND: METHODS: All patients who underwent molecular analysis of PCF between March 2013 and June 2015 were reviewed, including pathology, imaging, and follow-up. Molecular testing was performed using a patented, anchored multiplex polymerase chain reaction next-generation sequencing (NGS) platform, which sequenced numerous hotspots in 39 genes linked with malignancy. Performance of NGS and cytology was calculated using final outcome, as determined by clinicopathologic follow-up. RESULTS: The study cohort included 113 PCFs from 105 patients. In total, 119 variants were detected in 67 PCFs (59%). Variants were more common in intraductal papillary mucinous neoplasms (IPMNs)/ cancer than in nonmucinous cysts (P < .005). The inclusion of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)/ guanine nucleotide- binding protein (GNAS) variants improved the classification of IPMNs as mucinous from 50% by microscopy to 100%. Seventy-five percent of cancers had high-grade atypia versus 0% of IPMNs and nonmucinous cysts (P < .002). Variants in tumor protein 53 (TP53), SMAD family member 4 (SMAD4), cyclin-dependent kinase inhibitor 2A (CDKN2A), and notch1 (NOTCH1) were detected only in malignant cysts. Cytology was similarly specific (100%) for detecting malignant cysts but was more sensitive than the identification of late mutations by NGS (75% vs 46%). CONCLUSIONS: The detection of KRAS/GNAS variants improves the identification of mucinous neoplasms. Variants in TP53, SMAD4, CDKN2A, and NOTCH1 support the diagnosis of a high-risk cyst requiring surgery or additional sampling. Although molecular analysis is not a replacement for cytopathology, it does provide valuable information for accurate preoperative diagnosis, helping to classify mucinous neoplasms and high-risk cysts that require surgical resection. Cancer Cytopathol 2017;125:41-47. © 2016 American Cancer Society.
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Authors | Matthew W Rosenbaum, Martin Jones, Jonathan C Dudley, Long P Le, A John Iafrate, Martha B Pitman |
Journal | Cancer cytopathology
(Cancer Cytopathol)
Vol. 125
Issue 1
Pg. 41-47
(Jan 2017)
ISSN: 1934-6638 [Electronic] United States |
PMID | 27647802
(Publication Type: Journal Article)
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Copyright | © 2016 American Cancer Society. |
Chemical References |
- Biomarkers, Tumor
- Carcinoembryonic Antigen
- Neoplasm Proteins
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Topics |
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Biomarkers, Tumor
(genetics)
- Carcinoembryonic Antigen
(genetics)
- Cyst Fluid
(metabolism)
- Cystadenoma, Mucinous
(diagnosis, genetics, surgery)
- Cytodiagnosis
- Female
- High-Throughput Nucleotide Sequencing
- Humans
- Male
- Middle Aged
- Mutation
- Neoplasm Proteins
(genetics)
- Pancreatic Cyst
(diagnosis, genetics, pathology)
- Preoperative Period
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