Biological markers of tumorigenesis in human atherosclerotic plaques

A.M.Lavezzi MD,1, F.Flenda MD,2 A.Basellini MD,2 L.Matturri MD1

1Institute of Pathology and 2Institute of Vascular Surgery - University of Milan, Italy

AIM - Atherosclerotic plaques develop as a consequence of alternate cycles of vascular wall injuries (high levels of low-density lipoproteins, hyperthension, cigarette smoking, etc.) and repair. Cell proliferation, particularly of the SMCs, is believed to be one of the fundamental mechanism in the atherosclerotic process leading to the intimal hyperplasia. The aim of this study was to clarify the biological nature of the atherosclerotic lesions, through the investigation of several markers that are implicate in the pathogenesis of numerous proliferative diseases, including cancer. METHODS - In order to evaluate a similarity between atherogenic and carcinogenic processes, we investigated with immunohistochemical technique the c-fos proto-oncogene activation, p53 over-expression and proliferating cell nuclear antigen (PCNA) positivity in 35 patients undergoing to atherectomy for symptomatic and asymptomatic carotid artery stenosis. RESULTS - Overall, 40% of the examined atherosclerotic plaques revealed the presence of SMCs with p53 protein over-expression, 31% showed positive immunostaining for PCNA and 56% c-fos activation. An interesting finding was the correlation between c-fos and PCNA. In fact the cases with c-fos positivity were PCNA negative and vice versa. The joined presence of both these biomarkers was observed only in patients with previous episodes of ictus or transient ischaemic attacks. CONCLUSIONS - We believe that PCNA expression in atherosclerotic plaques, would be anticipated by c-fos proto-oncogene activation, which stimulates cell division. The joined presence of SMCs with both c-fos and PCNA positivity could be a signal of remarkable reactivation of the atherogenetic process. These findings indicate an important role of cancer biomarkers in vascular biology.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Diagnostic Markers.