Insulinoma-Associated Protein 1 (INSM1) as a Novel Immunohistochemical Marker for Neuroendocrine Neoplasms

Abstract Background: Diagnosis of neuroendocrine differentiation is important for tumor classification in different body systems. Confirmation of neuroendocrine differentiation, sometimes require immunohistochemistry (IHC) where morphology is not enough. Conventional immunohistochemical Neuroendo-crine markers are used as complementary tools for the diagnosis of NETs, however sometimes all of them are negative and the diagnosis could still be a challenge. In this regard, different studies were performed on insulinoma-associated protein 1 (INSM1) as a novel and helpful immunohistochemical marker for neuroendocrine neoplasms with higher sensitivity and specificity. Aim of Study: This study aims at proving the significance of INSM1 as a novel NE marker and to prove its superiority to other conventional NE markers. Material and Methods: The current study is carried out on 102 cases of different neuroendocrine tumors paraffin blocks that were collected from Pathology Department, Faculty of Medicine, Cairo University & private labs between January 2016 & January 2020. Formalin fixed paraffin-embedded sections of 4 microns thickness were cut on positively charged glass slides and immunostained using INSM1 mouse mono-clonal antibody. Another neuroendocrine marker (synapto-physin and/or chromogranin A) was done for confirmation of diagnosis & Ki-67 for grading. Results: Positive nuclear expression of INSM1 was de-tected in 90 cases (88%). 41.2% score 1, 40.2% score 2, 6.9% score 3. Negative expression was detected in the remaining 12 cases with significant relation between score of INSM1 and tumor site. Conclusion: In summary, we confirmed INSM1 expression in a large data set including pituitary adenomas, head and neck NET, lung NET, Mediastinal NET, GI NET, and pancre-atic NET, and found high sensitivity for detecting neuroendo-crine differentiation as compared with the currently established markers.