Comparative study of seven neuroendocrine markers in pancreatic endocrine tumours

A comparative immunocytochemical investigation was performed on a series of 59 pancreatic endocrine tumours using a panel of seven markers for neuroendocrine neoplasms: neurone specific enolase (NSE), PGP 9.5, chromogranin A (CgA), PHE5, prealbumin (Pa), HISL-19, and alpha-subunit of human chorionic gonadotropin (alpha-HCG). Most markers can be separated into two groups characterized by an identical immunoreactive cellular compartment and substantial overlapping in the immunohistochemical results. The first group comprises soluble cytoplasmic proteins such as NSE and PGP 9.5 and is characterized by a diffuse, homogeneous staining of the cell cytoplasm that is not related to the type of hormone produced or the degree of cell differentiation. The second group includes antigens located in the cell secretory granules such as CgA, PHE5, Pa and HISL-19 and is characterized by a heterogenous, often polarized cell staining. The latter markers strongly react with benign glucagonomas and PP-omas and, in contrast with those of the former group, are strictly neuroendocrine-specific. However, they often are less effective in staining insulinomas and malignant tumours. An additional, distinctive and useful characteristic of the HISL-19 antibody was its ability to label the Golgi complex also in tumours with absent granular staining. Finally, alpha-HCG was found in 9 of 16 malignant tumours (mostly glucagonomas and insulinomas) and in 4 of 43 benign neoplasms (all insulinomas). The latter finding is not in accordance with the reputed specificity of the alpha-HCG expression by pancreatic endocrine tumours as a marker for tumour malignancy.