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.