Selected markers (chromogranin A, neuron-specific enolase, synaptophysin, protein gene product 9.5) in diagnosis and prognosis of neuroendocrine pulmonary tumours

Abstract

Neuroendocrine tumours of lungs represent a subgroup of pulmonary tumours with typical morphofunctional traits. In light microscopy, the four principal types of the tumours (typical and atypical carcinoids, small cell lung cancer, large cell neuroendocrine carcinoma) demonstrate typical arrangement of cells (organoid nesting, palisading, a trabecular pattern, and rosette-like structures), variable number of mitoses, presence or absence of necrosis. In ultrastructure, neuroendocrine tumours manifest groups of cells with cytoplasmic granules (and the so called dense-core neurosecretory granules in particular). Neuroendocrine cells release hormones to circulation or in a paracrine manner. Some pulmonary tumours exhibit no neuroendocrine morphology at the level of light microscopy but demonstrate ultrastructural and/or immunohistochemical traits of neuroendocrine differentiation. Proteins the presence of which confirms neuroendocrine origin of the tumours have been found relatively early to include neuron-specific enolase (NSE), the group of chromogranins and synaptophysin. Present study aimed at summing up results of investigations conducted in, approximately, recent 30 years pertaining expression and/or serum concentrations of four neuroendocrine markers (chromogranin A, neuron-specific enolase, synaptophysin, protein gene product 9.5) and at an attempt to evaluate the role of such studies in extension of diagnostic and prognostic potential as related to neuroendocrine pulmonary tumours. Until now, the most sensitive and specific marker or marker combination for early detection of neuroendocrine subtypes of lung tumours has not been identified. All of the markers examined in present study were detected both in the typical neuroendocrine pulmonary tumours and in a certain proportion of non-endocrine tumours. In the case of chromogranin A improved sensitivity and specificity of immunocytochemical studies was obtained using a panel of antibodies directed to various epitopes of the protein. Both in endocrine and non-endocrine tumours, neuron-specific enolase (NSE) is thought to represent mainly a prognostic index, and only quantitation of serum concentrations of the protein or of the fraction of immunopositive cells may permit to differentiate between subtypes of the tumours. Synaptophysin is regarded to represent one of the most specific markers of neuroendocrine differentiation, manifesting a much higher sensitivity than chromogranin A and NSE. With increasing frequency, PGP 9.5 is regarded to provide a prognostic marker in diagnosis of non-small cell lung carcinomas rather than of typical neuroendocrine tumours.