Abstract 5434: Insulinoma-associated protein 1 (INSM1) expression in small cell neuroendocrine carcinoma of the urinary tract

Abstract

Abstract Introduction Clinical guidelines including the American Urological Association (AUA) state that neoadjuvant chemotherapy should be administered prior to surgery in cases of muscle invasive urinary bladder small cell neuroendocrine carcinoma. Although the recently described marker insulinoma-associated protein 1 (INSM1) has been reported to be sensitive and specific for neuroendocrine differentiation in neuroendocrine tumors at several sites, its efficacy as a marker in urinary bladder small cell carcinoma has not been well established. This study aims to examine the immunohistochemical expression pattern of INSM1 on whole tissue sections of urinary bladder small cell neuroendocrine carcinoma and compare INSM1 expression to those of established markers of neuroendocrine differentiation. Methods Archived tissue from 32 cases of urinary bladder small cell neuroendocrine carcinoma were obtained from Rhode Island Hospital and The Miriam Hospital. Immunohistochemical stains for CD56, INSM1, synaptophysin, and chromogranin were performed. Staining was scored for intensity (0: no staining; 1: weak; 2: moderate; 3: strong) and proportion of cells stained (0: 0%; 1: >0 to 25%; 2: >25 to 50%; 3: >50 to 75%; 4: >75 to 100%). Results INSM1 was positive (intensity 1-3 or proportion 1-4) in 87% (28/32) of small cell neuroendocrine carcinoma cases (20 with intensity 2-3, 17 with proportion 3-4). CD56, synaptophysin, and chromogranin were positive in 75% (24/32), 60% (19/32), and 44% (14/32) of cases, respectively. While the rate of positivity was high, INSM1 was negative (n=4) or only showed weak intensity staining (n=7) in 34% (11/32) of cases. Conclusion INSM1 is a sensitive marker of small cell neuroendocrine differentiation of the urinary bladder. However, the findings in this study suggest that optimal utilization of INSM1 would be in a limited panel of stains rather than as a stand-alone screening marker given that it is negative or only shows weak intensity staining in a significant proportion of cases. StainNegative [n (%)]Positive [n (%)]INSM14 (13)28 (87)CD568 (25)24 (75)Synaptophysin13 (40)19 (60)Chromogranin18 (56)14 (44) Citation Format: Isaac E. Kim, Ali Amin, Li Juan Wang, Liang Cheng, Carmen M. Perrino. Insulinoma-associated protein 1 (INSM1) expression in small cell neuroendocrine carcinoma of the urinary tract [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5434.