Insulinoma-associated protein 1 (INSM1), is a zinc-finger transcription factor, encoded by the gene INSM1. It plays a vital role in neuroendocrine differentiation, as a transcriptional repressor and a regulator of the cell cycle. INSM1 is expressed in developing neuroendocrine tissues during embryogenesis but also in neuroendocrine tumours. Recent studies have shown that INSM1 is a sensitive marker for the diagnosis of neuroendocrine tumours. Aim of the study: The goal of this study was to

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... ate INSM1 expression in primary small cell lung carcinomas (SCLCs), in order to evaluate its sensitivity as a marker against NCAM CD56 and synaptophysin markers that are widely used. Methods: Thirty one SCLC cases were retrieved from the archive of the Pathology Department. Small biopsies (formalin-fixed paraffin-embedded tissues, FFPET), histologically confirmed as SCLC, were used. Immunohistochemical staining with antibodies against INSM1, synaptophysin, CD56, TTF-1, CKAE1/AE3 and MIB1 was performed on the SCLC samples. Evaluation of the immunohistochemical stains was performed semi-quantitatively. Results: INSM1 immunostaining is characterised by a high sensitivity (31/31, 100%) for the diagnosis of SCLC, compared to other neuroendocrine markers such as synaptophysin and CD56 (29/31, 93.5%). Two SCLC cases were positive for INSM1 but negative, regarding synaptophysin and CD56 immunoexpressions. 24 of the 31 (77.4%) cases of SCLCs showed a strong/diffuse pattern of INSM1, which was better than that of synaptophysin in terms of distribution and intensity. Τhe intensity of nuclear staining on positive cells was high and nonspecific reactions were minimal. Intense cell proliferation was observed, with an index of MIB1 of 80% and above. Pankeratin AE1/AE3 showed the characteristic dot like distribution pattern. Positive immunostaining of TTF-1 was detected in 25/31 (80.6%) of SCLC cases. Nuclear immunostaining of INSM1 was easier to interpret in small biopsies, even in areas where extensive crush artifact is observed. Conclusion: INSM1 nuclear immunostaining can be a useful and a low cost marker in the diagnosis of SCLCs compared with traditional, cytoplasmic neuroendocrine markers like synaptophysin and CD56.