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Expression of neuroendocrine markers in non-small cell lung cancer: A biochemical, immunohistochemical and ultrastructural study

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Sørhaug S, Steinshamn S, Haaverstad R, Nordrum IS, Martinsen TC, Waldum HL. Expression of neuroendocrine markers in non-small cell lung cancer. A biochemical, immunohistological and ultrastructural study. APMIS 2007;115:152–63.

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.

Keywords: Immunoelectron microscopy; neuroendocrine differentiation; neuroendocrine markers; non-small cell lung cancer; tyramide signal amplification

Document Type: Research Article


Publication date: February 1, 2007


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