title: Expression of neuroendocrine markers in non-small cell lung cancer.
abstract: Neuroendocrine (NE) differentiation is reported in some cases of non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the expression of NE markers in NSCLC using novel sensitive methods. 20 cases of NSCLC were examined using immunohistochemical (IHC) and immunoelectron microscopy (IEM) methods. In addition, circulating levels of the NE markers chromogranin A (CgA) and neuron-specific enolase (NSE) were measured. Using conventional IHC methods, two tumours (10%) showed immunoreactivity for synaptophysin (SYN), one (5%) for Cg and four (20%) for neural cell adhesion molecule (NCAM). Adding the tyramide signal amplification (TSA) technique, the number of immunoreactive tumours for both SYN and CgA increased to five (25%). No increased immunoreactivity was achieved for NCAM. Nine tumours (45%) were immunoreactive for SYN, CgA or NCAM. Using IEM, one of five representative samples that revealed IHC reactivity for CgA showed immunogold labelling of CgA in cytoplasmic vesicles. Elevated levels of circulating CgA or NSE did not correlate with positive IHC findings. In conclusion, using sensitive IHC methods NE differentiation was seen in a greater proportion of NSCLC than previously reported. Sensitive methods may improve our understanding of the tumour biology and represent an important diagnostic tool for future therapeutic modalities.
authors.affiliation: Department of Circulation and Medical Imaging, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. sveinung.sorhaug@ntnu.no
authors.forename: Sveinung
authors.initials: S
authors.lastname: Sørhaug
authors.forename: Sigurd
authors.initials: S
authors.lastname: Steinshamn
authors.forename: Rune
authors.initials: R
authors.lastname: Haaverstad
authors.forename: Ivar S
authors.initials: IS
authors.lastname: Nordrum
authors.forename: Tom C
authors.initials: TC
authors.lastname: Martinsen
authors.forename: Helge L
authors.initials: HL
authors.lastname: Waldum
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000648:ultrastructure; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D018287:Carcinoma, Large Cell / Q000473:pathology / Q000648:ultrastructure; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology* / Q000648:ultrastructure; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000648:ultrastructure; D002648:Child; D053379:Chromogranin A / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000473:pathology* / Q000648:ultrastructure; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000032:analysis; D012907:Smoking; D016708:Synaptophysin / Q000032:analysis
chemical_list: D015415:Biomarkers; D053379:Chromogranin A; D016708:Synaptophysin; D010751:Phosphopyruvate Hydratase