title: Simultaneous multi-antibody staining in non-small cell lung cancer strengthens diagnostic accuracy especially in small tissue samples.
abstract: 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.
authors: Institute of Pathology, University Hospital Freiburg, Freiburg, Germany. gian.kayser@uniklinik-freiburg.de
authors: Gian
authors: G
authors: Kayser
authors: Agnes
authors: A
authors: Csanadi
authors: Claudia
authors: C
authors: Otto
authors: Till
authors: T
authors: Plönes
authors: Nicola
authors: N
authors: Bittermann
authors: Justyna
authors: J
authors: Rawluk
authors: Bernward
authors: B
authors: Passlick
authors: Martin
authors: M
authors: Werner
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D019002:CD56 Antigen / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000378:metabolism*; D053379:Chromogranin A / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D009687:Nuclear Proteins / Q000032:analysis; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013194:Staining and Labeling; D016708:Synaptophysin / Q000032:analysis; D000074482:Thyroid Nuclear Factor 1; D046888:Tissue Array Analysis / Q000379:methods; D014157:Transcription Factors / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis; D014746:Vimentin / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D019002:CD56 Antigen; D053379:Chromogranin A; C522918:NCAM1 protein, human; D009687:Nuclear Proteins; D016708:Synaptophysin; C115051:TP63 protein, human; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014746:Vimentin