The Utility of Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A) in the Differential Diagnosis of Pancreatic Cystic Neoplasms

ObjectiveThis study aims to evaluate the diagnostic utility of hypoxia inducible factor 1 subunit alpha (HIF1A) and carbonic anhydrase 9 (CA9) expression in differentiating between the 3 main types of pancreatic cystic neoplasms (PCNs): serous cystic neoplasms (SCNs), mucinous cystic neoplasms (MCNs), and intraductal papillary mucinous neoplasms (IPMNs).MethodsA retrospective analysis was conducted on 72 surgically resected PCNs (35 SCNs, 23 MCNs, and 14 IPMNs). Immunohistochemical staining for HIF1A and CA9 was performed and scored semi-quantitatively. HIF1A and CA9 mRNA expression levels were also quantified using qRT-PCR. Statistical analyses correlated biomarker expression with detailed clinicopathological features and patient survival.ResultsHIF1A mRNA expression was significantly higher in SCNs compared to MCNs and IPMNs (P < .001). Immunohistochemically, HIF1A protein was detected in 27 SCNs (77%) but was absent in all MCNs and IPMNs. In contrast, CA9 expression was frequently observed across all 3 PCN types (91% of SCNs, 96% of MCNs, and 86% of IPMNs) and showed no significant differential value.ConclusionHIF1A expression is a specific immunohistochemical marker for SCNs, reflecting underlying VHL/HIF pathway dysregulation and aiding in their distinction from mucinous PCNs (MCNs and IPMNs). CA9 lacks diagnostic specificity. Incorporating HIF1A assessment into diagnostic algorithms could improve the preoperative classification and management of PCNs.