Transmembrane protein tyrosine phosphatase IA-2 (ICA512) is expressed in human midgut carcinoids but is not detectable in normal enterochromaffin cells

A potential upregulation of receptor type protein tyrosine phosphatase IA-2 (ICA512) expression was detected by differential display and investigated in midgut carcinoid tumours. Normal intestine tissue and tumour tissue from 13 midgut carcinoid patients were studied by in situ hybridisation using a n IA-2 ribonucleotide probe and confocal microscopy using specific IA-2 ant ibodies. Previously, it had been shown that IA-2 is located in the secretor y granules of virtually all neuroendocrine cells. However, we found that IA -2 was not detectable in resting normal enterochromaffin (EC) cells of the small intestine, while high expression of IA-2 mRNA and protein was confirm ed in both primary and metastatic carcinoid tissue. This difference in expr ession was not observed with chromogranin A or serotonin, two secretory gra nule hormones known to be expressed in EC cells, indicating that IA-2 was s eemingly not necessary for the basal production and packaging of these horm ones. When comparing patients receiving biotherapy before operation with un treated patients, we found expression of IA-2 to be lower in tumours from p atients that had been treated with a combination of alpha-interferon and th e somatostatin analogue, octreotide. There was no correlation between IA-2 expression and proliferation rates as measured by immunohistochemistry with antibodies against the Ki 67 antigen. Furthermore, we show that IA-2 is co -localised with serotonin in carcinoid tumours as well as in the pancreatic tumour cell line, BON1, which is interesting as serotonin secretion rate i s presumably higher in tumour cells than in resting EC cells. Taken togethe r, these findings may indicate a role for IA-2 in the later stages of the r egulated secretory process.