Most adrenocortical
tumors (ACTs) can be diagnosed directly by a combination of morphologic features and clinical findings. However, sometimes it may be difficult to distinguish ACTs from other
neoplasms such as
pheochromocytomas and some metastatic
tumors, particularly for small biopsy specimens because they may be morphologically similar. Expression of
calretinin has recently been suggested as a valuable immunomarker for the differential diagnosis between ACTs and other
tumors; however, its diagnostic value is still under debate. To determine the diagnostic value of
calretinin in Chinese patients with adrenocortical and non-ACTs, we employed both polyclonal and monoclonal anticalretinin to characterize the expression of
calretinin in adrenal tissues and compared its expression with that of
inhibin alpha,
Melan-A,
cytokeratin, or CD99 by immunohistochemistry in tissue microarrays and standard tissue sections of 414 specimens. Our results revealed that
calretinin was expressed by adrenocortical cells, but not by the other cells tested and the percentage of
calretinin-positive ACTs reached 99% when stained with polyclonal
antibodies, which was higher than that with monoclonal anticalretinin (91.3%), anti-
Melan-A (90.3%), antiinhibin alpha (81.6%). In addition, our results also revealed that ACTs were stained by
cytokeratin (AE1/AE3) with variable degrees (58.7%). Furthermore, unlike anti-
Melan-A that stained all metastatic
malignant melanoma, anticalretinin did not recognize other tested
tumors. Therefore, immunohistologic staining with polyclonal anticalretinin is more sensitive than other
antibodies tested for the diagnosis of ACTs. However, monoclonal anticalretinin appeared to be more specific. Importantly, our data suggested that the fried-egg-like staining pattern, but not the mere cytoplasmic staining, was characteristic of anticalretinin staining in adrenocortical tissues. Notably, a few anticalretinin negative-ACTs were stained by other immunomarkers that we tested. Thus, the combinational characterization of
calretinin (either by polyclonal or
monoclonal antibody),
inhibin alpha, and
Melan-A expression is of great significance in the differential diagnosis of ACTs.