Investigation of HNF-1B as a diagnostic biomarker for pancreatic ductal adenocarcinoma
Abstract Background Diagnosing pancreatic ductal adenocarcinoma (PDAC) in the setting of metastasis with an unknown primary remains very challenging due to the lack of specific biomarkers. HNF-1B has been characterized as an important transcription factor for pancreatic development and was reported...
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doaj-d8c95c357fdd4130b6ff95e5e817e7b92020-11-24T22:01:23ZengBMCBiomarker Research2050-77712018-07-01611710.1186/s40364-018-0139-6Investigation of HNF-1B as a diagnostic biomarker for pancreatic ductal adenocarcinomaMichelle X. Yang0Ryan F. Coates1Abiy Ambaye2Juli-Anne Gardner3Richard Zubarick4Yuan Gao5Joan Skelly6James G. Liu7Mari Mino-Kenudson8Department of Pathology and Laboratory Medicine, University of Vermont Medical CenterDepartment of Pathology and Laboratory Medicine, University of Vermont Medical CenterDepartment of Pathology and Laboratory Medicine, University of Vermont Medical CenterDepartment of Pathology and Laboratory Medicine, University of Vermont Medical CenterGastroenterology, University of Vermont Medical CenterDepartment of Gastrointestinal Surgery, Nanjing Medical University affiliated Changzhou 2nd People’s HospitalUniversity of Vermont Medical Biostatistics DepartmentApplied Pathology SystemsDepartment of Pathology, Massachusetts General HospitalAbstract Background Diagnosing pancreatic ductal adenocarcinoma (PDAC) in the setting of metastasis with an unknown primary remains very challenging due to the lack of specific biomarkers. HNF-1B has been characterized as an important transcription factor for pancreatic development and was reported as a biomarker for clear cell subtype of PDAC. Methods To investigate the diagnostic role of HNF-1B for PDAC, we used tissue microarray (TMA) and immunohistochemistry (IHC) to characterize HNF-1B expression in a large cohort of carcinomas, including 127 primary PDACs, 47 biliary adenocarcinomas, 17 metastatic PDACs, and 231 non-pancreaticobiliary carcinomas. Results HNF-1B was expressed in 107 of 127 (84.3%) of PDACs, 13 of 15 (86.7%) of cholangiocarcinomas, 13 of 18 (72%) of ampullary carcinomas, and 13 of 14 (92.9%) of gallbladder adenocarcinomas. Notably, HNF-1B was expressed in 16 of 17 (94.1%) of metastatic PDACs. Among the non-pancreaticobiliary cancers, HNF-1B was expressed in ~ 77% clear cell carcinomas of the kidney and ovarian clear cell carcinomas. Gastroesophageal, lung, and prostate adenocarcinomas occasionally expressed HNF-1B in up to 37% cases. HNF-1B was completely negative in hepatocellular, colorectal, breast, and lung squamous cell carcinomas. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of HNF-1B for primary pancreaticobiliary carcinoma is 84, 68, 66, 85, and 75%, respectively. HNF-1B expression was not significantly associated with overall survival in patients with PDAC, but tumor size ≥2 cm and high tumor grade were significantly associated with worse overall survival in multivariate analyses. Conclusions HNF-1B may be used in surgical pathology to aid the diagnosis of metastatic pancreatic and biliary carcinoma with a panel of other markers to exclude lung, kidney, prostate, and Müllerian origins.http://link.springer.com/article/10.1186/s40364-018-0139-6HNF-1BPancreaticPancreaticobiliaryAdenocarcinomaTissue microarrayImmunohistochemistry |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Michelle X. Yang Ryan F. Coates Abiy Ambaye Juli-Anne Gardner Richard Zubarick Yuan Gao Joan Skelly James G. Liu Mari Mino-Kenudson |
spellingShingle |
Michelle X. Yang Ryan F. Coates Abiy Ambaye Juli-Anne Gardner Richard Zubarick Yuan Gao Joan Skelly James G. Liu Mari Mino-Kenudson Investigation of HNF-1B as a diagnostic biomarker for pancreatic ductal adenocarcinoma Biomarker Research HNF-1B Pancreatic Pancreaticobiliary Adenocarcinoma Tissue microarray Immunohistochemistry |
author_facet |
Michelle X. Yang Ryan F. Coates Abiy Ambaye Juli-Anne Gardner Richard Zubarick Yuan Gao Joan Skelly James G. Liu Mari Mino-Kenudson |
author_sort |
Michelle X. Yang |
title |
Investigation of HNF-1B as a diagnostic biomarker for pancreatic ductal adenocarcinoma |
title_short |
Investigation of HNF-1B as a diagnostic biomarker for pancreatic ductal adenocarcinoma |
title_full |
Investigation of HNF-1B as a diagnostic biomarker for pancreatic ductal adenocarcinoma |
title_fullStr |
Investigation of HNF-1B as a diagnostic biomarker for pancreatic ductal adenocarcinoma |
title_full_unstemmed |
Investigation of HNF-1B as a diagnostic biomarker for pancreatic ductal adenocarcinoma |
title_sort |
investigation of hnf-1b as a diagnostic biomarker for pancreatic ductal adenocarcinoma |
publisher |
BMC |
series |
Biomarker Research |
issn |
2050-7771 |
publishDate |
2018-07-01 |
description |
Abstract Background Diagnosing pancreatic ductal adenocarcinoma (PDAC) in the setting of metastasis with an unknown primary remains very challenging due to the lack of specific biomarkers. HNF-1B has been characterized as an important transcription factor for pancreatic development and was reported as a biomarker for clear cell subtype of PDAC. Methods To investigate the diagnostic role of HNF-1B for PDAC, we used tissue microarray (TMA) and immunohistochemistry (IHC) to characterize HNF-1B expression in a large cohort of carcinomas, including 127 primary PDACs, 47 biliary adenocarcinomas, 17 metastatic PDACs, and 231 non-pancreaticobiliary carcinomas. Results HNF-1B was expressed in 107 of 127 (84.3%) of PDACs, 13 of 15 (86.7%) of cholangiocarcinomas, 13 of 18 (72%) of ampullary carcinomas, and 13 of 14 (92.9%) of gallbladder adenocarcinomas. Notably, HNF-1B was expressed in 16 of 17 (94.1%) of metastatic PDACs. Among the non-pancreaticobiliary cancers, HNF-1B was expressed in ~ 77% clear cell carcinomas of the kidney and ovarian clear cell carcinomas. Gastroesophageal, lung, and prostate adenocarcinomas occasionally expressed HNF-1B in up to 37% cases. HNF-1B was completely negative in hepatocellular, colorectal, breast, and lung squamous cell carcinomas. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of HNF-1B for primary pancreaticobiliary carcinoma is 84, 68, 66, 85, and 75%, respectively. HNF-1B expression was not significantly associated with overall survival in patients with PDAC, but tumor size ≥2 cm and high tumor grade were significantly associated with worse overall survival in multivariate analyses. Conclusions HNF-1B may be used in surgical pathology to aid the diagnosis of metastatic pancreatic and biliary carcinoma with a panel of other markers to exclude lung, kidney, prostate, and Müllerian origins. |
topic |
HNF-1B Pancreatic Pancreaticobiliary Adenocarcinoma Tissue microarray Immunohistochemistry |
url |
http://link.springer.com/article/10.1186/s40364-018-0139-6 |
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