Phaeochromocytomas overexpress insulin transcript and produce insulin
Introduction: Phaeochromocytomas are tumours originating in the medulla of the adrenal gland. They produce catecholamines and some tumours also produce ectopic hormones. Production of insulin has not been reported. However, two types of glucose imbalances occur in pheaochromocytoma patients, hyperglycaemia and hypoglycaemic attacks. Therefore, we tested whether insulin was expressed in phaeochromocytomas. Methods: We measured the expression of insulin using immunohistochemistry. The expression of insulin transcript (INS) and a hybrid read-through transcript between exons from insulin and insulin-like growth factor 2 (INS-IGF2) was determined by qRT-PCR in formalin-fixed and paraffin-embedded tissue from 20 phaeochromocytomas. The expression of INS and INS-IGF2 transcripts was also analysed in 182 phaeochromocytomas and paragangliomas using publicly available datasets in The Cancer Genome Atlas (TCGA) Database. Results: Of 20 phaeochromocytomas, 16 stained positive for insulin. The distribution of positive cells was mostly scattered, with some focal expression indicating clonal expansion. 19 tumours expressed high levels of INS and INS-IGF2 transcripts. The expression of the two transcripts correlated positively. In the TCGA dataset, phaeochromocytoma express higher levels of INS and INS-IGF2 transcripts compared to normal non-tumour adrenal gland tissue (p=0.01). Thus, expression of INS and INS-IGF2 seems to be a general phenomenon in phaeochromocytoma. Conclusion: Most phaeochromocytomas contain cells that express the INS and INS-IGF2 transcripts. As most tumours also express polypeptides immunoreactive to monoclonal anti-insulin antibodies, expression of the transcripts are likely functionally relevant. Clinically this may relate to both hyperglycaemia and hypoglycaemic attacks seen in patients with a phaeochromocytoma.