Triple marker composed of p16, CD56, and TTF1 shows higher sensitivity than INSM1 for diagnosis of pulmonary small cell carcinoma: proposal for a rational immunohistochemical algorithm for diagnosis of small cell carcinoma in small biopsy and cytology specimens
Language English Country United States Media print-electronic
Document type Journal Article
PubMed
30385371
DOI
10.1016/j.humpath.2018.10.016
PII: S0046-8177(18)30413-1
Knihovny.cz E-resources
- Keywords
- Cytology, INSM1, Immunohistochemistry, Small cell lung cancer, p16,
- MeSH
- Algorithms MeSH
- CD56 Antigen metabolism MeSH
- Biopsy MeSH
- DNA-Binding Proteins metabolism MeSH
- Adult MeSH
- Immunohistochemistry MeSH
- Cyclin-Dependent Kinase Inhibitor p16 metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Small Cell Lung Carcinoma diagnosis metabolism pathology MeSH
- Biomarkers, Tumor metabolism MeSH
- Lung Neoplasms diagnosis metabolism pathology MeSH
- Repressor Proteins metabolism MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Sensitivity and Specificity MeSH
- Transcription Factors metabolism MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- CD56 Antigen MeSH
- CDKN2A protein, human MeSH Browser
- DNA-Binding Proteins MeSH
- Cyclin-Dependent Kinase Inhibitor p16 MeSH
- INSM1 protein, human MeSH Browser
- Biomarkers, Tumor MeSH
- Repressor Proteins MeSH
- Transcription Factors MeSH
- TTF1 protein, human MeSH Browser
Pulmonary small cell carcinoma (SCLC) can be usually diagnosed based on the morphological evaluation of routine histological or cytological preparations. However, immunohistochemistry may be also necessary in problematic cases. Insulinoma-associated 1 (INSM1) has recently been reported as a highly sensitive and specific marker that displays positivity in ~90%-100% of poorly differentiated pulmonary neuroendocrine tumors. We compared diagnostic performance of INSM1 and previously reported composite marker CD56 + p16 + thyroid transcription factor-1 (TTF1) in the diagnosis of SCLC in small biopsy specimens and cytoblocks. The composite marker CD56 + p16 + TTF1 correctly classified 100% of SCLC cases, and its sensitivity was significantly higher than the sensitivity of INSM1. Among 100 SCLC cases, CD56, TTF1, and p16 each individually classified more specimens correctly than INSM1 (CD56: 84%, TTF1: 89%, p16: 95%, INSM1: 81%); the difference was statistically significant only for p16. INSM1 showed the lowest classification agreement between paired biopsy and cytoblock specimens (κ = 0.182), whereas CD56 and p16 displayed perfect agreement (κ = 1) and TTF1 showed moderate agreement (κ = 0.4). Although INSM1 is reportedly the most specific marker of SCLC, its sensitivity is not superior to p16 or composite marker CD56 + TTF1 + p16. Based on this study, we propose the following algorithm, which, in the appropriate clinical and histological context, may be useful in establishing the correct diagnosis of SCLC: First, INSM1 detection is performed, and if the result is negative, CD56 is added, followed successively by p16 and TTF1 if all previously applied markers are negative. This approach should detect most, if not all, SCLC cases, while successively trading specificity for sensitivity.
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