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.
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.
['Švajdler|Marián|M|', 'Mezencev|Roman|R|', 'Šašková|Bohuslava|B|', 'Ondič|Ondrej|O|', 'Mukenšnábl|Petr|P|', 'Michal|Michal|M|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000465:Algorithms D014408:Biomarkers, Tumor D001706:Biopsy D019002:CD56 Antigen D019941:Cyclin-Dependent Kinase Inhibitor p16 D004268:DNA-Binding Proteins D005260:Female D006801:Humans D007150:Immunohistochemistry D008175:Lung Neoplasms D008297:Male D008875:Middle Aged D012097:Repressor Proteins D012680:Sensitivity and Specificity D055752:Small Cell Lung Carcinoma D014157:Transcription Factors
p16 INSM1 Cytology Immunohistochemistry Small cell lung cancer