The Clinical Relevance of Recent Developments in Pathology and Biology of Small Cell Lung Cancer: Specific peptides

In: Lung Cancer

15 Nov 2014

The Clinical Relevance of Recent Developments in Pathology and Biology of Small Cell Lung Cancer: Specific peptidesB. Specific peptides: Multiple peptides have been demonstrated in SCLC tumors based on immunohistochemistry. At present the literature is loaded with studies using different antibodies, which hampers an interpretation of the results. Bombesin or the mammalian homologue, gastrin-releasing peptide (GRP), has attracted considerable interest. It acts apparently as an autocrine growth factor for SCLC, and it is noteworthy that the growth of SCLC cells in vitro and in xenografts can be inhibited by a monoclonal antibody to GRP” While GRP has been demonstrated frequently in experimental models, it has been difficult to identify this peptide on formalin-fixed surgical material.

The frequencies of bombesin-like immunoreactivity based on immunocytochemistry vary considerably. Said et al observed 9 of 13 SCLC tumors to be positive, Bostwick et al found only 1 of 8 SCLC tumors, while Kameya et al demonstrated GRP-positive staining in 27% of 48 SCLC tumors. The discrepancies may be due to the use of different antibodies and to different fixation and embedding techniques. GRP alone seems at present to be of little value for routine histopathologic diagnostics. More recently, the interest has turned to pro-GRP, which seems to be detectable much more frequently on formalin-fixed paraffin-embedded SCLC tumors than GRP While most of the studies using immunohistochemistry have found bombesin-like immunoreactivity focally and only moderately strong in about 25% of SCLC, the antibodies to the C-terminal peptide of human probombesin showed strong and diffuse immunostaining in 70% of 250 SCLC tumors. Accordingly, the pro-GRP may be a much better diagnostic marker than the GRP. Link

ACTH has by many authors been stressed to be one of the peptide immunoreactivities most commonly associated with SCLC, but the frequencies vary considerably from study to study. One main reason may be that nearly all the ACTH studies fail to report the region- or site-specificity of the antibodies used. ACTH has also been demonstrated in non-SCLC tumors and the diagnostic value of this peptide in the histopathologic classification still remains to be identified. Apart from “bombesin” and ACTH, numerous other peptides may be associated with SCLC. Thus, calcitonin, vasopressin, somatostatin, physalaemine, substance P, and neurotensin have all been demonstrated mainly in SCLG-cell lines but also in non-SCLC cell lines. The potential role of these markers in the histopathologic diagnosis of malignant lung tumors remains to be identified.

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