Expression of activin and inhibin subunits, receptors and binding proteins in human pheochromocytomas: A study based on mRNA analysis and immunohistochemistry

Objective: Pheochromocytomas are uncommon tumours arising from chromaffin cells of the adrenal medulla and related paraganglia. So far, one of the few reported markers to discriminate malignant from benign tumours is the βB-subunit of inhibin and activin, members of the transforming growth factor (TGF)-β superfamily of growth and differentiation factors. Design: We investigated the expression of the mRNAs coding for activin and inhibin subunits, their receptors and binding proteins by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and studied the presence of the inhibin βB-subunit in human pheochromocytomas by immunohistochemistry. Patients: Samples from resected pheochromocytomas of patients operated between 1973 and 2003 were used for experiments. Results: The immunohistochemical investigations revealed that staining of the inhibin βB-subunit was positive in 12 of 36 (33%) benign and 5 of 34 (15%) malignant pheochromocytomas (P > 0.05). Therefore, it was not possible to discriminate between benign and malignant tumours solely on the basis of inhibin βB-subunit immunohistochemistry. Quantitative real-time RT-PCR in nine benign and four malignant tumours showed expression of inhibin α-, βA- and βB-subunits, the activin receptors Alk-4, ActRIIA, and ActRIIB, and the inhibin- and activin-binding proteins betaglycan and follistatin in all samples. No correlations were detected between individually coupled expression of mRNAs of these activin- and inhibin-related genes in the 13 pheochromocytomas. Only inhibin βA-subunit expression was different in malignant compared to benign pheochromocytomas (P = 0.020). Conclusions: No clear role for activin and inhibin was found in discriminating between benign and malignant pheochromocytomas.