Investigation of HNF-1B as a diagnostic biomarker for pancreatic ductal adenocarcinoma

Abstract

BackgroundDiagnosing 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.MethodsTo 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.ResultsHNF-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.ConclusionsHNF-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.

Primary Clear Cell Carcinoma of the Pancreas: A Systematic Review

“…An interesting study was published in 2018 by Yang and colleagues, whereby they sought to investigate the presence of a marker that could provide an accurate diagnosis of pancreatic adenocarcinoma [ 26 ]. They chose HNF1B due to its developmental role during pancreatic morphogenesis and were keen to prove that its expression is present in all types of adenocarcinomas of the pancreas.…”

A case of MODY5-like manifestations without mutations or deletions in coding and minimal promoter regions of the <i>HNF1B</i> gene

“…We also failed to detect mutations in the minimal promoter region of the HNF1B gene (-580 bp relative to the initiator ATG codon). Human HNF1B is known to be expressed in pancreatic ductal epithelium cells and centroacinar cells and intercalated ductal cells with predominant nuclear and faint cytoplasmic staining [12]. Immunohistochemical analysis using anti-HNF1B antibody (Catalogue number HPA002083, Atlas antibodies) found expression of HNF1B protein in some pancreatic cells including ductal epithelium cells and possibly MODY5-like syndrome without HNF1B defect centroacinar cells and intercalated ductal cells ( Fig.…”

HNF-1β is a More Sensitive and Specific Marker Than C-Reactive Protein for Identifying Biliary Differentiation in Primary Hepatic Carcinomas

“…17 Studies show that pancreatic ductal adenocarcinoma expresses HNF-1b in 75.6% to 84.3% of cases. 6 In the liver, HNF-1b expression in iCCAs and its correlation with expression of other biliary markers has been reported. [18][19][20] However, the significance of HNF-1b expression in hepatic malignancies and its clinical utility remains controversial.…”

“…5 Hepatocyte nuclear factor-1b (HNF-1b) is a transcription factor that plays a critical role in normal development of the kidney, biliary tract, and pancreas. 6,7 Mutations in HNF-1b can cause pancreatic agenesis or hypoplasia, cholestasis, abnormal intrahepatic bile duct differentiation and morphogenesis, hypoplastic glomerulocystic kidney, and genital tract malformations. [8][9][10] In human malignancies, HNF-1b has been shown to be expressed in ovarian clear cell carcinomas, endometrial carcinomas, colorectal carcinomas, clear cell renal cell carcinomas, and urothelial carcino-mas.…”