Subtyping of Undifferentiated Non-small Cell Carcinomas in Bronchial Biopsy Specimens

The emergence of treatments for non-small cell lung carcinoma (NSCLC) with differential efficacy and toxicity between subtypes has highlighted the importance of specific pathologic NSCLC subtyping. Most NSCLCs are inoperable, and pathologic diagnosis is made only on small tissue samples that are pro...

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Veröffentlicht in:Journal of thoracic oncology 2010-04, Vol.5 (4), p.442-447
Hauptverfasser: Loo, Peh Sun, Thomas, Stuart C., Nicolson, Marianne C., Fyfe, Margaret N., Kerr, Keith M.
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container_issue 4
container_start_page 442
container_title Journal of thoracic oncology
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creator Loo, Peh Sun
Thomas, Stuart C.
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Fyfe, Margaret N.
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description The emergence of treatments for non-small cell lung carcinoma (NSCLC) with differential efficacy and toxicity between subtypes has highlighted the importance of specific pathologic NSCLC subtyping. Most NSCLCs are inoperable, and pathologic diagnosis is made only on small tissue samples that are prone to diagnostic inaccuracy. In a substantial proportion of cases, standard morphology cannot specifically subtype the tumor, necessitating a diagnosis of NSCLC-not otherwise specified (NOS). Histochemical staining for mucin and immunohistochemical (IHC) identification of NSCLC subtype-associated markers could help predict the final subtype of resected NSCLCs diagnosed as NSCLC-NOS on preoperative bronchial biopsy samples. Paraffin sections of 44 bronchial biopsy samples diagnosed as NSCLC-NOS were stained for mucin (Alcian blue/periodic acid Schiff) and thyroid transcription factor 1 by IHC–(markers of adenocarcinoma), and for S100A7, cytokeratin 5/6, high molecular weight cytokeratins, and p63 proteins–markers of squamous cell carcinoma. A predictive staining panel was derived from statistical analysis after comparing staining profiles with the final postsurgical NSCLC subtype. This panel was prospectively applied to 82 small biopsy samples containing NSCLC. True NSCLC subtype of undifferentiated NSCLC samples was best predicted using Alcian blue/periodic acid Schiff plus p63 and thyroid transcription factor 1 IHC, allowing specific subtyping in 73% of NSCLC-NOS cases with 86% accuracy. When applied prospectively, this staining panel showed 100% concordance with specific NSCLC morphologic subtyping in small biopsies. This approach can facilitate treatment selection by accurately predicting the subtype in undifferentiated NSCLC biopsies, reducing to 7% the proportion of cases without a definite or probable histologic subtype.
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Most NSCLCs are inoperable, and pathologic diagnosis is made only on small tissue samples that are prone to diagnostic inaccuracy. In a substantial proportion of cases, standard morphology cannot specifically subtype the tumor, necessitating a diagnosis of NSCLC-not otherwise specified (NOS). Histochemical staining for mucin and immunohistochemical (IHC) identification of NSCLC subtype-associated markers could help predict the final subtype of resected NSCLCs diagnosed as NSCLC-NOS on preoperative bronchial biopsy samples. Paraffin sections of 44 bronchial biopsy samples diagnosed as NSCLC-NOS were stained for mucin (Alcian blue/periodic acid Schiff) and thyroid transcription factor 1 by IHC–(markers of adenocarcinoma), and for S100A7, cytokeratin 5/6, high molecular weight cytokeratins, and p63 proteins–markers of squamous cell carcinoma. A predictive staining panel was derived from statistical analysis after comparing staining profiles with the final postsurgical NSCLC subtype. 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subjects Adenocarcinoma - classification
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Biomarkers, Tumor - metabolism
Biopsy, Fine-Needle
Bronchi - metabolism
Bronchi - pathology
Bronchial biopsy diagnosis
Carcinoma, Large Cell - classification
Carcinoma, Large Cell - metabolism
Carcinoma, Large Cell - pathology
Carcinoma, Non-Small-Cell Lung - classification
Carcinoma, Non-Small-Cell Lung - metabolism
Carcinoma, Non-Small-Cell Lung - pathology
Carcinoma, Squamous Cell - classification
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
Cell Differentiation
Humans
Immunoenzyme Techniques
Immunohistochemistry
Keratin-5 - metabolism
Keratin-6 - metabolism
Lung Neoplasms - classification
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Mucins - metabolism
Neoplasm Staging
Non-small cell lung carcinoma
NSCLC subtype
NSCLC-NOS
Nuclear Proteins - metabolism
p63
Predictive value
Prognosis
Prospective Studies
S100 Calcium Binding Protein A7
S100 Proteins - metabolism
Sensitivity and Specificity
Survival Rate
Thyroid Nuclear Factor 1
Trans-Activators - metabolism
Transcription Factors - metabolism
TTF1
Tumor Suppressor Proteins - metabolism
Undifferentiated carcinoma
title Subtyping of Undifferentiated Non-small Cell Carcinomas in Bronchial Biopsy Specimens
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