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[12] Utility of C4D Immunohistochemistry in Acute Myocardial Infarction

C Jenkins, D Cardona, S Normann. University of Florida, Gainesville, FL

Background: The pathologic presence of acute myocardial infarction (AMI) is determined by gross and histological examination. These findings are generally not seen early in the course of an AMI (<9-12 hours). The earliest indication of cell death is contraction band necrosis, which can be seen within minutes of reperfusion. However, it is often absent in typical infarction and is considered an artifact in endomyocardial biopsies. C4d (and C3d) is an end-product of the classical complement cascade which covalently binds the target tissue. The utility of C4d immunohistochemistry (IHC) is well described in the evaluation of antibody-mediated rejection of cardiac allografts. Full activation and involvement of the complement pathway following AMI has been shown. The aim of our study is to determine the specificity and potential timeline in C4d detection on necrotic myocytes following an AMI.
Design: Sixteen autopsy cases with a total of 26 areas of infarcted myocardium were reviewed. The clinical record and microscopic examination of H&E slides showed that the areas of infarction ranged from a few hours to months in age. IHC was performed on paraffin sections of formalin-fixed tissue using the ABC/peroxidase method with C4d. Staining patterns and intensity were recorded. Five cases without evidence of infarction were used as controls and histologically normal myocardium functioned as an internal control.
Results: C4d antibody strongly and diffusely stained necrotic myocytes in all cases of 8 to 48 hours in age (10/10). Adjacent histologically normal myocytes were nonreactive, resulting in clear delineation of damaged myocardium by C4d. Four cases with only scattered contraction band necrosis showed focal to no C4d reactivity, indicating that contraction bands may not be specific for necrotic myocytes. Three cases with 3-7 day old infarcts showed variable staining. Areas of fragmented myocytes showed focal weak staining. Infarctions of >1-2 months and negative controls were nonreactive. The use of C4d provided new diagnoses in two cases, including evidence of reinfarction and a newly diagnosed AMI.
Conclusions: C4d is specific for necrotic myocytes as areas of histologically apparent necrosis stained strongly for C4d and normal appearing myocytes did not. C4d staining of necrotic myocytes is apparent prior to the influx of inflammatory cells making this a useful diagnostic tool in the event of uncertainty. The contrast achieved by IHC impressively creates a clear delineation between viable and necrotic myocytes, making C4d an efficient diagnostic tool.
Category: Autopsy

Monday, March 3, 2008

Poster # 8, Monday Morning