Comparison of INSM1 immunostaining with established neuroendocrine markers Synaptophysin and Chromogranin A in over 14,000 neuroendocrine and non-neuroendocrine tumors

Abstract Introduction/Objective INSM1 is a transcription factor protein which is increasingly used as an immunohistochemical marker for neuroendocrine differentiation. Methods/Case Report To determine the prevalence of INSM1 expression in tumors and its expression pattern in normal tissues, tissue microarrays containing 14,908 samples from 117 different tumor types/subtypes as well as 76 different normal tissues were analyzed by immunohistochemistry. Results (if a Case Study enter NA) INSM1 was positive in 89.2% of 471 neuroendocrine neoplasms (NEN) and in 3.5% of 11,815 non-neuroendocrine neoplasms that were successfully analyzed. INSM1 positivity occurred in 59 non- neuroendocrine tumor entities, of which 15 entities contained at least one strongly positive case. Comparison with synaptophysin and chromogranin A revealed that in NEN, synaptophysin showed the highest sensitivity (93.3%), followed by INSM1 (89.2%) and chromogranin A (87.5%). In neuroendocrine carcinomas (NEC), sensitivity was highest for INSM1 (88.0%), followed by synaptophysin (86.5%) and chromogranin A (66.4%). The additional use of INSM1 increased the sensitivity for detecting neuroendocrine differentiation in NEN from 88.2% (synaptophysin and chromogranin A) to 91.2% (synaptophysin, chromogranin A and INSM1). Conclusion Our study shows that INSM1 is a useful additional marker for neuroendocrine differentiation that shows a particularly high sensitivity in NEC. The additional use of INSM1 results in a higher sensitivity for the identification of a neuroendocrine differentiation than what can be obtained by using only synaptophysin and chromogranin A.