Immunohistochemical expression of Ki67, c-erbB-2, and c-kit antigens in benign and malignant pheochromocytoma.

In this study, we evaluated the immunohistochemical expression and the possible advantages of Ki67 antigen, c-erbB-2, and c-kit proto-oncogenes in the differentiation between benign and malignant pheochromocytomas. Paraffin-embedded tissue blocks from 44 benign (35 adrenal and 9 extra-adrenal) and 11 malignant (9 adrenal and 2 extra-adrenal) cases of pheochromocytoma were selected for immunohistochemical staining using antibodies against Ki67, c-erbB-2, and c-kit antigens. We investigated the relationship between the expression of these antigens and age, gender, tumor size, histologic patterns and necrosis, as well as tumor behavior. The risk of malignancy was higher when tumor size was increased. We found out that more uncommon tissue patterns, such as small cell and spindle cell patterns, are mostly indicators of malignancy. There was a statistically significant relationship between Ki67- and c-erbB-2-positive staining of the tumor cells and the malignant behavior of the pheochromocytomas (p-value=0.000), while cytoplasmic c-kit staining did not show any correlation with tumor malignancy (p-value=0.087). We concluded that tumor size and the histomorphologic patterns (spindle cell and small round cell) are significantly associated with tumor behavior. In addition, Ki67 positivity and c-erbB-2 expression can be used as immunohistochemical markers for predicting the malignant behavior of pheochromocytoma.