Simultaneous multi-antibody staining in non-small cell lung cancer strengthens diagnostic accuracy especially in small tissue samples.

Histological subclassification of non-small cell lung cancer (NSCLC) has growing therapeutic impact. In advanced cancer stages tissue specimens are usually bioptically collected. These small samples are of extraordinary value since molecular analyses are gaining importance for targeted therapies. We...

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Main Authors: Gian Kayser, Agnes Csanadi, Claudia Otto, Till Plönes, Nicola Bittermann, Justyna Rawluk, Bernward Passlick, Martin Werner
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3572034?pdf=render
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author Gian Kayser
Agnes Csanadi
Claudia Otto
Till Plönes
Nicola Bittermann
Justyna Rawluk
Bernward Passlick
Martin Werner
author_facet Gian Kayser
Agnes Csanadi
Claudia Otto
Till Plönes
Nicola Bittermann
Justyna Rawluk
Bernward Passlick
Martin Werner
author_sort Gian Kayser
collection DOAJ
description Histological subclassification of non-small cell lung cancer (NSCLC) has growing therapeutic impact. In advanced cancer stages tissue specimens are usually bioptically collected. These small samples are of extraordinary value since molecular analyses are gaining importance for targeted therapies. We therefore studied the feasibility, diagnostic accuracy, economic and prognostic effects of a tissue sparing simultaneous multi-antibody assay for subclassification of NSCLC. Of 265 NSCLC patients tissue multi arrays (TMA) were constructed to simulate biopsy samples. TMAs were stained by a simultaneous bi-color multi-antibody assay consisting of TTF1, Vimentin, p63 and neuroendocrine markers (CD56, chromogranin A, synaptophysin). Classification was based mainly on the current proposal of the IASLC with a hierarchical decision tree for subclassification into adenocarcinoma (LAC), squamous cell carcinoma (SCC), large cell neuroendocrine carcinoma (LCNEC) and NSCLC not otherwise specified. Investigation of tumor heterogeneity showed an explicit lower variation for immunohistochemical analyses compared to conventional classification. Furthermore, survival analysis of our combined immunohistochemical classification revealed distinct separation of each entity's survival curve. This was statistically significant for therapeutically important subgroups (p = 0.045). As morphological and molecular cancer testing is emerging, our multi-antibody assay in combination with standardized classification delivers accurate and reliable separation of histomorphological diagnoses. Additionally, it permits clinically relevant subtyping of NSCLC including LCNEC. Our multi-antibody assay may therefore be of special value, especially in diagnosing small biopsies. It futher delivers substantial prognostic information with therapeutic consequences. Integration of immunohistochemical subtyping including investigation of neuroendocrine differentiation into standard histopathological classification of NSCLC must, therefore, be considered.
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spelling doaj.art-b48506469dcb4ee492e2516d4ee005152022-12-21T19:04:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5633310.1371/journal.pone.0056333Simultaneous multi-antibody staining in non-small cell lung cancer strengthens diagnostic accuracy especially in small tissue samples.Gian KayserAgnes CsanadiClaudia OttoTill PlönesNicola BittermannJustyna RawlukBernward PasslickMartin WernerHistological subclassification of non-small cell lung cancer (NSCLC) has growing therapeutic impact. In advanced cancer stages tissue specimens are usually bioptically collected. These small samples are of extraordinary value since molecular analyses are gaining importance for targeted therapies. We therefore studied the feasibility, diagnostic accuracy, economic and prognostic effects of a tissue sparing simultaneous multi-antibody assay for subclassification of NSCLC. Of 265 NSCLC patients tissue multi arrays (TMA) were constructed to simulate biopsy samples. TMAs were stained by a simultaneous bi-color multi-antibody assay consisting of TTF1, Vimentin, p63 and neuroendocrine markers (CD56, chromogranin A, synaptophysin). Classification was based mainly on the current proposal of the IASLC with a hierarchical decision tree for subclassification into adenocarcinoma (LAC), squamous cell carcinoma (SCC), large cell neuroendocrine carcinoma (LCNEC) and NSCLC not otherwise specified. Investigation of tumor heterogeneity showed an explicit lower variation for immunohistochemical analyses compared to conventional classification. Furthermore, survival analysis of our combined immunohistochemical classification revealed distinct separation of each entity's survival curve. This was statistically significant for therapeutically important subgroups (p = 0.045). As morphological and molecular cancer testing is emerging, our multi-antibody assay in combination with standardized classification delivers accurate and reliable separation of histomorphological diagnoses. Additionally, it permits clinically relevant subtyping of NSCLC including LCNEC. Our multi-antibody assay may therefore be of special value, especially in diagnosing small biopsies. It futher delivers substantial prognostic information with therapeutic consequences. Integration of immunohistochemical subtyping including investigation of neuroendocrine differentiation into standard histopathological classification of NSCLC must, therefore, be considered.http://europepmc.org/articles/PMC3572034?pdf=render
spellingShingle Gian Kayser
Agnes Csanadi
Claudia Otto
Till Plönes
Nicola Bittermann
Justyna Rawluk
Bernward Passlick
Martin Werner
Simultaneous multi-antibody staining in non-small cell lung cancer strengthens diagnostic accuracy especially in small tissue samples.
PLoS ONE
title Simultaneous multi-antibody staining in non-small cell lung cancer strengthens diagnostic accuracy especially in small tissue samples.
title_full Simultaneous multi-antibody staining in non-small cell lung cancer strengthens diagnostic accuracy especially in small tissue samples.
title_fullStr Simultaneous multi-antibody staining in non-small cell lung cancer strengthens diagnostic accuracy especially in small tissue samples.
title_full_unstemmed Simultaneous multi-antibody staining in non-small cell lung cancer strengthens diagnostic accuracy especially in small tissue samples.
title_short Simultaneous multi-antibody staining in non-small cell lung cancer strengthens diagnostic accuracy especially in small tissue samples.
title_sort simultaneous multi antibody staining in non small cell lung cancer strengthens diagnostic accuracy especially in small tissue samples
url http://europepmc.org/articles/PMC3572034?pdf=render
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