Fibronectin expression as a marker of hypoxia in asphyxial deaths: A pilot study

• Fibronectin marks hypoxic stress in the myocardium of asphyxial deaths. • Fibronectin expression varies across asphyxia subtypes and mechanisms. • Fibronectin remodeling reveals cellular responses beyond gross findings. • Fibronectin can support diagnosis when macroscopic signs are inconclusive. • Fibronectin paves the way for molecular tools in forensic pathology. Asphyxial deaths represent a major diagnostic challenge in forensic practice, as classical morphological signs are nonspecific and may overlap with other causes of sudden death. Fibronectin (FN), an extracellular matrix glycoprotein sensitive to hypoxia, is emerging as a candidate biomarker of oxygen deprivation. We investigated its expression in cardiac tissue from asphyxial deaths compared with traumatic controls. We retrospectively collected formalin-fixed, paraffin-embedded left ventricular myocardium from autopsies in Palermo and Genoa (2021–2025). The cohort included 54 cases: 45 asphyxial deaths (5 smothering, 4 strangulation, 15 hanging, 17 drowning, 4 chemical asphyxia) and 9 non-asphyxial traumatic controls. We performed FN immunohistochemistry (IHC) with a monoclonal antibody and quantified FN-positive cardiomyocytes using dedicated image-analysis software. We found significantly higher FN expression in all asphyxial deaths compared with controls (mean 11.7 ± 3.6%). The highest intensities were observed in smothering (46.1 ± 7.2%) and strangulation (45.0 ± 8%), followed by chemical asphyxia (35.1 ± 9.8%), hanging (27.8 ± 6.6%), and drowning (21.4 ± 5.9%). FN levels varied between subgroups, but their consistent elevation confirms its reliability as a marker of hypoxic injury in asphyxia. FN upregulation in the myocardium is a consistent hallmark of asphyxial deaths, reflecting extracellular matrix changes under hypoxia. FN identifies hypoxic stress rather than mechanism-specific asphyxia; nonetheless, it can be a valuable aid in forensic diagnosis, especially when morphology alone is inconclusive. Integration of FN IHC with conventional autopsy and histology could enhance diagnostic accuracy and support medicolegal assessments of asphyxial death.