Department of Pathology
Amino Acids, Peptides, and Proteins | Biological Factors | Diagnosis | Immunopathology | Investigative Techniques | Neoplasms | Pathological Conditions, Signs and Symptoms | Pathology
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 Mullerian origins.
Adenocarcinoma, HNF-1B, Immunohistochemistry, Pancreatic, Pancreaticobiliary, Tissue microarray
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© The Author(s). 2018 Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
DOI of Published Version
Biomark Res. 2018 Jul 27;6:25. doi: 10.1186/s40364-018-0139-6. eCollection 2018. Link to article on publisher's site
Yang MX, Coates RF, Ambaye A, Gardner J, Zubarick R, Gao Y, Skelly J, Liu JG, Mino-Kenudson M. (2018). Investigation of HNF-1B as a diagnostic biomarker for pancreatic ductal adenocarcinoma. Open Access Articles. https://doi.org/10.1186/s40364-018-0139-6. Retrieved from https://escholarship.umassmed.edu/oapubs/3550
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This work is licensed under a Creative Commons Attribution 4.0 License.
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