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

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 \u3e /=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

Transition to Subspecialty Sign-Out at an Academic Institution and Its Advantages

Many pathology departments are introducing subspecialty sign-out in surgical pathology. In 2014, the University of Vermont Medical Center transitioned from general sign-out to partial subspecialty sign-out to include gastrointestinal and breast/cervix subspecialty benches; other specimens remained on general benches. Our experiences with the transition are described, including attending pathologist, trainee, support staff, and clinician satisfaction. A survey was e-mailed to all University of Vermont Medical Center anatomic pathology attendings, pathology trainees, pathologist assistants and grossing technicians, and clinicians who send surgical pathology specimens, immediately before and 1 year after transitioning to partial subspecialty sign-out. Quality assurance metrics were obtained for the 18 months prior to and following the transition. Gastrointestinal and breast/cervix attendings were more satisfied with partial subspecialty sign-out compared to those on the general benches. Overall, trainees were more satisfied with general sign-out because of the rotation schedule but preferred partial subspecialty sign-out due to improved teaching and more focused learning while on subspecialty benches. Clinicians remained very satisfied with our department and our reports; no differences were observed. Turnaround time was unchanged. After switching to partial subspecialty sign-out, there were significantly fewer discrepancies following multidisciplinary conference review for gastrointestinal and breast/cervix cases but remained the same for general cases. Fewer formal internal consults were performed after transitioning to partial subspecialty sign-out across all areas, but more notable for gastrointestinal and breast/cervix cases. Our data show improved quality assurance metrics and trainee education in a subspecialty sign-out setting compared to general sign-out setting