INSM1 Is Less Sensitive But More Specific Than Synaptophysin in Gynecologic High-grade Neuroendocrine Carcinomas: An Immunohistochemical Study of 75 Cases With Specificity Test and Literature Review

Insulinoma-associated protein 1 (INSM1) has emerged as a promising diagnostic marker for high-grade neuroendocrine carcinomas (HGNECs); however, it is controversial whether INSM1 is more sensitive than conventional markers chromogranin, synaptophysin, and CD56. Here, we investigated immunohistochemical expression of INSM1 in 75 gynecologic HGNECs using full tissue sections (30 small-cell carcinomas [SmCCs], 34 large-cell neuroendocrine carcinomas [LCNECs], and 11 mixed SmCC and LCNEC), with specificity analysis in 422 gynecologic non-neuroendocrine tumors (410 in tissue microarrays and 12 full sections) and comparison with conventional neuroendocrine markers for their sensitivity and specificity. Positive INSM1 staining was seen in 69 (92%) HGNECs, whereas chromogranin, synaptophysin, and CD56 staining was seen in 61 (81%), 72 (96%), and 44 (69%) tumors, respectively (INSM1 vs. chromogranin, P=0.09; INSM1 vs. synaptophysin, P=0.4942; and INSM1 vs. CD56, P