title: The role of calretinin, inhibin, melan-A, BCL-2, and C-kit in differentiating adrenal cortical and medullary tumors: an immunohistochemical study.
abstract: Morphologic distinction between adrenal cortical and medullary tumors can be difficult. Previous studies have shown inhibin, melan-A, and BCL-2 to be useful markers for adrenal cortical tumors. We have recently observed a high level of calretinin expression in normal adrenal cortex but not the medulla and therefore evaluated its diagnostic application for adrenal tumors in comparison with inhibin, melan-A, and BCL-2. C-kit is a transmembrane tyrosine kinase receptor. Immunodetection of c-kit expression has been recently used for tumor diagnosis, and c-kit-positive tumors can potentially benefit from kit kinase inhibitor treatment. Although c-kit expression was reported in adrenal medulla and pheochromocytoma, it has not been evaluated in adrenal cortical tumors. In this study, 28 adrenal cortical tumors (12 carcinomas, 16 adenomas), 20 pheochromocytomas, and 20 extraadrenal paragangliomas were evaluated for calretinin, inhibin, melan-A, BCL-2, and c-kit expression by standard immunohistochemical assays on paraffin sections. The percentage of immunoreactivity in adrenal cortical tumors was as follows: calretinin, 96%; melan-A, 89%; inhibin, 92%; BCL-2, 20%; and c-kit, 5%. Normal adrenal medulla did not stain for c-kit but was positive for BCL-2. Eighty-six percent of pheochromocytomas stained for BCL-2 and none for calretinin, with the exception of the ganglioneuromatous areas in composite pheochromocytomas (n = 5). Extraadrenal paragangliomas showed reactivity with calretinin in 25%, melan-A in 5%, inhibin in 16%, BCL-2 in 38%, and c-kit in 8% of the cases. Our results indicate that calretinin is the most sensitive among all the adrenal markers tested. Like melan-A and inhibin, calretinin is also a very specific marker in differentiating cortical from medullary adrenal tumors. In addition, calretinin can be used to confirm a composite pheochromocytoma. BCL-2 does not appear to be useful in differentiating adrenal cortical from medullary tumors. C-kit is not useful in the diagnosis of adrenal tumors, and kit kinase inhibitor might have a limited role in the treatment of adrenal tumors and paraganglioma because of the low frequency of c-kit expression in these tumors.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19147, USA. pjz@mail.med.upenn.edu
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Zhang
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Genega
authors.forename: John E
authors.initials: JE
authors.lastname: Tomaszewski
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Pasha
authors.forename: Virginia A
authors.initials: VA
authors.lastname: LiVolsi
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000378:metabolism / Q000473:pathology*; D000313:Adrenal Medulla / Q000378:metabolism / Q000473:pathology*; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000378:metabolism; D064032:Calbindin 2; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D007265:Inhibins / Q000378:metabolism; D058965:MART-1 Antigen; D009363:Neoplasm Proteins / Q000378:metabolism; D010673:Pheochromocytoma / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C576764:CALB2 protein, human; D064032:Calbindin 2; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D064030:S100 Calcium Binding Protein G; D007265:Inhibins; D019009:Proto-Oncogene Proteins c-kit