Novel immunohistochemical assay utilizing the INSM1 (SP493) antibody demonstrates high specificity and sensitivity in detecting neuroendocrine lung tumors

Introduction : About 20% of lung cancers are of neuroendocrine origin. In addition to evaluation of morphological features, these neoplasms can be identified by immunohistochemistry (IHC) using antibodies against neuroendocrine markers such as synaptophysin, chromogranin A and neural cell adhesion molecule, CD56. Recent studies showed that INSM1 is increasingly used as a diagnostic marker for cancers of neuroendocrine origin, since it is highly sensitive and specific. The primary focus of this study was to evaluate the sensitivity and specificity of a recently developed assay that is using a new INSM1 (SP493) antibody for detecting neuroendocrine lung cancers and to compare this IHC assay with currently used neuroendocrine markers. Method : Tissue microarrays containing 391 lung tumors were stained with INSM1 (SP493) antibody, INSM1 (MRQ-70) antibody, CONFIRM anti-Synaptophysin (SP11) antibody, anti-Chromogranin A (LK2H10) antibody, and CD56 (MRQ-42) antibody on BenchMark ULTRA instruments using OptiView IHC DAB Detection Kit or ultraView Universal DAB Detection Kit using manufacturer’s recommended protocols. Sensitivity, specificity and accuracy were calculated for each biomarker.Results: The sensitivity and specificity of the new assay using INSM1 (SP493) antibody were 96.8% and 92.3%, respectively. Comparable results were seen for the lung cancer cases stained with INSM1 (MRQ-70) antibody; yielding a sensitivity of 94.9% and specificity of 94.1%. In contrast, the anti-Chromogranin A (LK2H10) antibody and CD56 (MRQ-42) antibody showed considerably lower sensitivities for detecting lung cancer cases with neuroendocrine differentiation. The sensitivity was 78.7% and 85.4% for anti-Chromogranin A (LK2H10) antibody and CD56 (MRQ-42) antibody, respectively. However, the specificities of anti-Chromogranin A (LK2H10) antibody and CD56 (MRQ-42) antibody were comparable with the specificity of the INSM1 (SP493) antibody [91.7% for anti-Chromogranin A (LK2H10), 90.4% for CD56 (MRQ-42) antibody]. The performance of anti-Synaptophysin (SP11) antibody was suboptimal with a sensitivity of 82.9% and a specificity of 87.6%. Conclusions : Overall, our data demonstrate that the IHC assay using the newly developed INSM1 (SP493) antibody is highly specific and sensitive for identifying neuroendocrine lung neoplasms.