DNA profile components predict malignant outcomes in select cases of intraductal papillary mucinous neoplasm with negative cytology

Rachel E. Simpson, Nathan J. Cockerill, Michele Yip-Schneider, Eugene P. Ceppa, Michael House, Nicholas Zyromski, Attila Nakeeb, Mohammad A. Al-Haddad, C. Schmidt

Research output: Contribution to journalArticle

Abstract

Background: Predicting malignancy in intraductal papillary mucinous neoplasm remains challenging. Integrated molecular pathology combines pancreatic fluid DNA and clinical factors into a malignant potential score. We sought to determine the utility of DNA components alone in predicting high-grade dysplasia/invasive disease. Methods: We reviewed prospectively the records from 1,106 patients with intraductal papillary mucinous neoplasm. We excluded non-intraductal papillary mucinous neoplasm cases and cases with definitive malignant cytology. A total 225 patients had 283 DNA profiles (98 followed by surgery, 185 followed by ≥23-month surveillance). High-grade dysplasia/invasive outcomes were high-grade dysplasia, intraductal papillary mucinous neoplasm-invasive, and adenocarcinoma on surgical pathology or mesenteric or vascular invasion, metastases, or biopsy with high-grade dysplasia or adenocarcinoma during surveillance. Results: High-quantity DNA predicted (P = .004) high-grade dysplasia/invasive disease outcomes with sensitivity of 78.3%, but 52.7% specificity, indicating benign cases may exhibit high-quantity DNA. High clonality loss of heterozygosity of tumor suppressor genes was 98.0% specific, strongly predicted high-grade dysplasia/invasive disease but lacked sensitivity (20.0%). High-quantity DNA + high clonality loss of heterozygosity had 99.0% specificity for high-grade dysplasia/invasive disease. KRAS mutation alone did not predict high-grade dysplasia/invasive disease, but, when combined with high-quantity DNA (specificity 84.7%) and high clonality loss of heterozygosity (specificity 99.0%) strongly predicted high-grade dysplasia/invasive outcomes. Conclusion: Certain DNA components are highly specific for high-grade dysplasia/invasive disease and may indicate aggressive lesions, requiring resection when cytology fails.

Original languageEnglish (US)
JournalSurgery (United States)
DOIs
StateAccepted/In press - Jan 1 2018

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Cell Biology
DNA
Loss of Heterozygosity
Neoplasms
Adenocarcinoma
Surgical Pathology
Molecular Pathology
Tumor Suppressor Genes
Blood Vessels
Neoplasm Metastasis
Biopsy
Mutation

ASJC Scopus subject areas

  • Surgery

Cite this

@article{701a84e4629248bab44a5bd579deb4c0,
title = "DNA profile components predict malignant outcomes in select cases of intraductal papillary mucinous neoplasm with negative cytology",
abstract = "Background: Predicting malignancy in intraductal papillary mucinous neoplasm remains challenging. Integrated molecular pathology combines pancreatic fluid DNA and clinical factors into a malignant potential score. We sought to determine the utility of DNA components alone in predicting high-grade dysplasia/invasive disease. Methods: We reviewed prospectively the records from 1,106 patients with intraductal papillary mucinous neoplasm. We excluded non-intraductal papillary mucinous neoplasm cases and cases with definitive malignant cytology. A total 225 patients had 283 DNA profiles (98 followed by surgery, 185 followed by ≥23-month surveillance). High-grade dysplasia/invasive outcomes were high-grade dysplasia, intraductal papillary mucinous neoplasm-invasive, and adenocarcinoma on surgical pathology or mesenteric or vascular invasion, metastases, or biopsy with high-grade dysplasia or adenocarcinoma during surveillance. Results: High-quantity DNA predicted (P = .004) high-grade dysplasia/invasive disease outcomes with sensitivity of 78.3{\%}, but 52.7{\%} specificity, indicating benign cases may exhibit high-quantity DNA. High clonality loss of heterozygosity of tumor suppressor genes was 98.0{\%} specific, strongly predicted high-grade dysplasia/invasive disease but lacked sensitivity (20.0{\%}). High-quantity DNA + high clonality loss of heterozygosity had 99.0{\%} specificity for high-grade dysplasia/invasive disease. KRAS mutation alone did not predict high-grade dysplasia/invasive disease, but, when combined with high-quantity DNA (specificity 84.7{\%}) and high clonality loss of heterozygosity (specificity 99.0{\%}) strongly predicted high-grade dysplasia/invasive outcomes. Conclusion: Certain DNA components are highly specific for high-grade dysplasia/invasive disease and may indicate aggressive lesions, requiring resection when cytology fails.",
author = "Simpson, {Rachel E.} and Cockerill, {Nathan J.} and Michele Yip-Schneider and Ceppa, {Eugene P.} and Michael House and Nicholas Zyromski and Attila Nakeeb and Al-Haddad, {Mohammad A.} and C. Schmidt",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.surg.2018.05.033",
language = "English (US)",
journal = "Surgery",
issn = "0039-6060",
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TY - JOUR

T1 - DNA profile components predict malignant outcomes in select cases of intraductal papillary mucinous neoplasm with negative cytology

AU - Simpson, Rachel E.

AU - Cockerill, Nathan J.

AU - Yip-Schneider, Michele

AU - Ceppa, Eugene P.

AU - House, Michael

AU - Zyromski, Nicholas

AU - Nakeeb, Attila

AU - Al-Haddad, Mohammad A.

AU - Schmidt, C.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Predicting malignancy in intraductal papillary mucinous neoplasm remains challenging. Integrated molecular pathology combines pancreatic fluid DNA and clinical factors into a malignant potential score. We sought to determine the utility of DNA components alone in predicting high-grade dysplasia/invasive disease. Methods: We reviewed prospectively the records from 1,106 patients with intraductal papillary mucinous neoplasm. We excluded non-intraductal papillary mucinous neoplasm cases and cases with definitive malignant cytology. A total 225 patients had 283 DNA profiles (98 followed by surgery, 185 followed by ≥23-month surveillance). High-grade dysplasia/invasive outcomes were high-grade dysplasia, intraductal papillary mucinous neoplasm-invasive, and adenocarcinoma on surgical pathology or mesenteric or vascular invasion, metastases, or biopsy with high-grade dysplasia or adenocarcinoma during surveillance. Results: High-quantity DNA predicted (P = .004) high-grade dysplasia/invasive disease outcomes with sensitivity of 78.3%, but 52.7% specificity, indicating benign cases may exhibit high-quantity DNA. High clonality loss of heterozygosity of tumor suppressor genes was 98.0% specific, strongly predicted high-grade dysplasia/invasive disease but lacked sensitivity (20.0%). High-quantity DNA + high clonality loss of heterozygosity had 99.0% specificity for high-grade dysplasia/invasive disease. KRAS mutation alone did not predict high-grade dysplasia/invasive disease, but, when combined with high-quantity DNA (specificity 84.7%) and high clonality loss of heterozygosity (specificity 99.0%) strongly predicted high-grade dysplasia/invasive outcomes. Conclusion: Certain DNA components are highly specific for high-grade dysplasia/invasive disease and may indicate aggressive lesions, requiring resection when cytology fails.

AB - Background: Predicting malignancy in intraductal papillary mucinous neoplasm remains challenging. Integrated molecular pathology combines pancreatic fluid DNA and clinical factors into a malignant potential score. We sought to determine the utility of DNA components alone in predicting high-grade dysplasia/invasive disease. Methods: We reviewed prospectively the records from 1,106 patients with intraductal papillary mucinous neoplasm. We excluded non-intraductal papillary mucinous neoplasm cases and cases with definitive malignant cytology. A total 225 patients had 283 DNA profiles (98 followed by surgery, 185 followed by ≥23-month surveillance). High-grade dysplasia/invasive outcomes were high-grade dysplasia, intraductal papillary mucinous neoplasm-invasive, and adenocarcinoma on surgical pathology or mesenteric or vascular invasion, metastases, or biopsy with high-grade dysplasia or adenocarcinoma during surveillance. Results: High-quantity DNA predicted (P = .004) high-grade dysplasia/invasive disease outcomes with sensitivity of 78.3%, but 52.7% specificity, indicating benign cases may exhibit high-quantity DNA. High clonality loss of heterozygosity of tumor suppressor genes was 98.0% specific, strongly predicted high-grade dysplasia/invasive disease but lacked sensitivity (20.0%). High-quantity DNA + high clonality loss of heterozygosity had 99.0% specificity for high-grade dysplasia/invasive disease. KRAS mutation alone did not predict high-grade dysplasia/invasive disease, but, when combined with high-quantity DNA (specificity 84.7%) and high clonality loss of heterozygosity (specificity 99.0%) strongly predicted high-grade dysplasia/invasive outcomes. Conclusion: Certain DNA components are highly specific for high-grade dysplasia/invasive disease and may indicate aggressive lesions, requiring resection when cytology fails.

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U2 - 10.1016/j.surg.2018.05.033

DO - 10.1016/j.surg.2018.05.033

M3 - Article

JO - Surgery

JF - Surgery

SN - 0039-6060

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