Immunohistochemical assessment of angiogenic and anti-angiogenic markers in pre-eclampsia: A clinical review of diagnostic and prognostic utility

Background: Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality worldwide. Central to its pathogenesis is abnormal placental development characterized by impaired angiogenesis and widespread endothelial dysfunction. Immunohistochemistry (IHC) provides a reliable method for visualizing and quantifying tissue-level expression of angiogenic and anti-angiogenic markers implicated in this multisystem disorder. This systematic review evaluates the immunohistochemical expression of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and soluble endoglin (sEng) in preeclamptic placentas, with particular emphasis on their diagnostic and prognostic relevance.

Methods: Comprehensive literature search was carried out across PubMed and Google Scholar, for published studies between 2013 and 2024. The review adhered to PRISMA guidelines and included observational studies that assessed placental immunohistochemical expression of selected angiogenic and anti-angiogenic markers in preeclamptic versus normotensive pregnancies. Extracted data included study design, sample size, staining methodology, expression patterns, and reported clinical outcomes.

Results: Fifteen eligible studies encompassing over 10,000 placental samples were included. Across studies, VEGF and PlGF expression were consistently reduced in preeclamptic placentas, whereas sFlt-1 and sEng expression were markedly elevated. Elevated expression of sFlt-1 and sEng correlated strongly with disease severity, adverse maternal outcomes, foetal growth restriction, and preterm delivery.

Conclusion: Immunohistochemical assessment of angiogenic imbalance provides valuable insight into the pathophysiology of preeclampsia and holds promise as an adjunctive diagnostic and prognostic tool. These findings reinforce the role of angiogenic dysregulation as a defining feature of preeclampsia and support continued integration of tissue-based biomarker evaluation into risk stratification strategies.