Reliability of commercially available immunocytochemical markers for identification of neuroendocrine differentiation in bronchoscopic biopsies of bronchial carcinoma

Abstract

Background - Although neuroendocrine differentiation occurs quite commonly in non-small cell bronchial malignancies, its biological significance and implications for management remain uncertain. Determining these facts requires its recognition early, ideally at diagnosis, which is usually made on tissue from bronchoscopy, but the best means of its detection in such material is unclear. A prospective comparative study was performed of 10 commercially available antisera to a series of markers of neuroendocrine differentiation, to test their efficacy when applied to fibreoptic bronchoscopy biopsy specimens. Methods - Expression of chromogranin A, synaptophysin, neurone- specific enolase, protein gene product 9.5, the BB isoenzyme of creatine kinase, gastrin releasing peptide, adrenocorticotrophic hormone, calcitonin, calcitonin gene related peptide, and leucine enkephalin was sought by immunolabelling of bronchoscopic biopsy tissue from 83 primary bronchial carcinomas, 22 of them of small cell type. Results - Only synaptophysin and chromogranin were sensitive and specific enough for neuroendocrine differentiation to discriminate between small cell and non-small cell lesions, whereas protein gene product 9.5 and creatine kinase were neither particularly sensitive nor specific and neurone-specific enolase actually labelled more non-small cell tumours than small cell lesions. Of the five secretory products sought, only gastrin releasing peptide was detectable in just one tumour. Three squamous and two morphologically undifferentiated tumours immunolabelled for synaptophysin and chromogranin, almost certainly indicating neuroendocrine differentiation in the absence of small cell morphology. Conclusions - Of the markers studied, only synaptophysin and chromogranin were sufficiently specific and sensitive for neuroendocrine differentiation to justify their inclusion in any panel of antibodies used in its detection in tissue obtained at fibreoptic bronchoscopy.