Expression of c-fos, p53 and PCNA in the unstable atherosclerotic carotid plaque

Background: The process by which a fibrofatty plaque evolves into a fibrotic lesion or into an unstable, lipid-rich plaque is poorly understood. In this study our aim is to deepen the knowledge of the cellular proliferation mechanisms that characterize the initial phases of destabilization of the unstable carotid plaque. Methods: 32 specimens from carotid endarterectomies were employed to assess by immunohistochemical methods, either in stable (n=10) or unstable (n=22) atherosclerotic plaques, the proliferating cell nuclear antigen (PCNA), the proto-oncogene c-fos, and the oncoprotein p53. Results: 18/32 atherosclerotic plaques (all unstable), showed c-fos immunopositivity (P<0.0001). Ten lesions, three stable and seven unstable, were PCNA+, while 13 cases were positive for p53 (three stable and 10 unstable plaques). When comparing symptomatic vs. asymptomatic patients, the most striking finding was the coincidence between c-fos, PCNA and p53 protein positivity observed only in unstable plaques of seven out of eight patients, all with previous episodes of stroke or transient ischemic attacks. On the other hand, none of the above mentioned positivity was detected in the 24 asymptomatic patients (P<0.0001). Conclusions: These findings indicate an important role of these biomarkers in vascular biology. A series of molecular pathways of disease development and progression common both to atherosclerosis and cancer, support that the world’s two most common diseases are more closely aligned than previously believed.