Immunohistochemical Evaluation of Amyloidosis in Endomyocardial Biopsies.
Carmela D Tan, Mazen Hanna, E Rene Rodriguez. Cleveland Clinic, OH
Background: Distinguishing between the different types of amyloid that involves the heart has become increasingly important for therapeutic purposes. While there are at least 27 different proteins that can form amyloid fibrils, the most commonly encountered in cardiac biopsies are immunoglobulin light chains (AL) and transthyretin (ATTR). The limitations of immunohistochemical typing of amyloid in biopsy specimens are well-known. We sought to investigate the utility of immunohistochemical staining in establishing the amyloid type found in endomyocardial biopsies.
Design: Fifty-five cases of amyloidosis were diagnosed on endomyocardial biopsies within a 36-month period. Thioflavin S stain was used to identify amyloid in paraffin-embedded tissue sections. Immunohistochemical staining using a panel of amyloid A, kappa, lambda and transthyretin was performed on all positive biopsies. Sequencing of the transthyretin gene from blood samples was performed in half of the patients with ATTR.
Results: Amyloid typing was possible in 52 of the 55 cases (94%). Two cases were negative for all 4 antibodies; diagnosis was established by electron microscopy in 1 of these cases. Staining results were equivocal in the third case. None of the cases stained with amyloid A. Occasional nonspecific weak staining with light chains was seen in ATTR cases. Conversely, transthyretin does not appear to cross-react with AL amyloidosis.
There is a marked predominance of male patients with amyloidosis of any type (overall M:F ratio is 4:1). Patients with ATTR (mean age 73) are older than AL patients (mean age 66). ATTR was the most common type of amyloid found (n=22), followed by AL of lambda light chains (n=19) and AL of kappa light chains (n=11). Six of 11 ATTR patients were positive for mutations in the transthyretin gene. The most common mutation was Val122Ile. Two of the ATTR patients with organ involvement limited to the heart underwent cardiac transplantation and are alive without disease on 2-year follow-up.
Conclusions: Immunohistochemistry diagnosis of amyloid in endomyocardial biopsies is a reliable method. Molecular genetic testing of transthyretin is a valuable complement to the work-up of these patients.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 31, Wednesday Afternoon