Insulinoma-associated Protein 1 (INSM1) is a Useful Marker for Pancreatic Neuroendocrine Tumor

Overview

Journal Med Mol Morphol

Publisher Springer

Specialties Cell Biology
Molecular Biology
Pathology

Date 2017 Aug 30

PMID 28849340

Citations 26

Authors

Masahiko Tanigawa

Masamichi Nakayama

Tomoki Taira

Satoshi Hattori

Yutaro Mihara

Reiichiro Kondo

Hironori Kusano

Ken Nakamura

Yushi Abe

Yusuke Ishida

Yoshinobu Okabe

Toru Hisaka

Koji Okuda

Kosuke Fujino

Takaaki Ito

Akihiko Kawahara

Yoshiki Naito

Rin Yamaguchi

Jun Akiba

Yoshito Akagi

Hirohisa Yano

Affiliations

Soon will be listed here.

Abstract

Insulinoma-associated protein 1 (INSM1) is an important biomarker of Achaete-scute homolog-like 1-driven pathways. For diagnosis of pancreatic neuroendocrine tumors (PanNET), chromogranin A (CGA), synaptophysin (SYP), and neural cell adhesion molecule (NCAM) were also considered as potential biomarkers. However, it is often difficult to diagnose it immunohistochemically. Hence, we examined the expression pattern of INSM1 in pancreatic solid tumors. We detected INSM1, CGA, SYP, and NCAM immunohistochemically, in 27 cases of NET [pure type: 25 cases, mixed adenoneuroendocrine carcinoma (MANEC): 2 cases]. We included 5 cases of solid-pseudopapillary neoplasm (SPN), 7 cases of acinar cell carcinoma (ACC), and 15 cases of pancreatic ductal adenocarcinoma (PDAC) as the control group. Nuclear expression of INSM1 was found in all PanNET pure type cases. However, expression of INSM1 was negative in PDAC, ACC, and SPN in all cases, whereas faint expression was seen in the cytoplasm from SPN. MANEC comprises of two components: neuroendocrine carcinoma and adenocarcinoma components. The NET component was positive for INSM1 expression, whereas the PDAC component does not express INSM1, which aids in distinguishing these components. Our results suggest that INSM1 is a useful immunohistochemical marker for diagnosing pancreatic neuroendocrine tumor.

Citing Articles

[Neuroendocrine tumors].

Chouchane A, Brautigam K, Perren A Pathologie (Heidelb). 2025; 46(2):127-136.

PMID: 39969551 PMC: 11861404. DOI: 10.1007/s00292-025-01415-z.

Comparison of insulinoma-associated protein 1 (INSM1) with traditional neuroendocrine markers in gastrointestinal and pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs).

Gao R, Zhang X, Chen X, Lin Y, Jin L, Zheng H Diagn Pathol. 2024; 19(1):144.

PMID: 39472993 PMC: 11520864. DOI: 10.1186/s13000-024-01568-0.

Insulinoma-associated protein-1 (INSM-1) is a useful diagnostic marker for the evaluation of primary thymic neuroendocrine neoplasms: an immunohistochemical study of 27 cases.

Suster D, Chacko D, VanderLaan P, Mino-Kenudson M, Hung Y Virchows Arch. 2024; .

PMID: 39223347 DOI: 10.1007/s00428-024-03904-7.

Comparison among different preclinical models derived from the same patient with a non-functional pancreatic neuroendocrine tumor.

Wang Y, Ye Z, Lou X, Xu J, Jing D, Zhou C Hum Cell. 2024; 37(5):1522-1534.

PMID: 39078546 DOI: 10.1007/s13577-024-01107-5.

INSM1 promotes breast carcinogenesis by regulating C-MYC.

Guan Y, Sun Y, Liu Z, Zhang Y, Cao M, Wang W Am J Cancer Res. 2023; 13(8):3500-3516.

PMID: 37693125 PMC: 10492136.

References

Goto Y, de Silva M, TOSCANI A, Prabhakar B, Notkins A, Lan M . A novel human insulinoma-associated cDNA, IA-1, encodes a protein with "zinc-finger" DNA-binding motifs. J Biol Chem. 1992; 267(21):15252-7. View

Notohara K, Hamazaki S, Tsukayama C, Nakamoto S, Kawabata K, Mizobuchi K . Solid-pseudopapillary tumor of the pancreas: immunohistochemical localization of neuroendocrine markers and CD10. Am J Surg Pathol. 2000; 24(10):1361-71. DOI: 10.1097/00000478-200010000-00005. View

Girardi D, Silva A, Rego J, Coudry R, Riechelmann R . Unraveling molecular pathways of poorly differentiated neuroendocrine carcinomas of the gastroenteropancreatic system: A systematic review. Cancer Treat Rev. 2017; 56:28-35. DOI: 10.1016/j.ctrv.2017.04.002. View

Basturk O, Yang Z, Tang L, Hruban R, Adsay V, McCall C . The high-grade (WHO G3) pancreatic neuroendocrine tumor category is morphologically and biologically heterogenous and includes both well differentiated and poorly differentiated neoplasms. Am J Surg Pathol. 2015; 39(5):683-90. PMC: 4398606. DOI: 10.1097/PAS.0000000000000408. View

Lan M, Breslin M . Structure, expression, and biological function of INSM1 transcription factor in neuroendocrine differentiation. FASEB J. 2009; 23(7):2024-33. PMC: 2704596. DOI: 10.1096/fj.08-125971. View

Hirabayashi K, Kurokawa S, Maruno A, Yamada M, Kawaguchi Y, Nakagohri T . Sex differences in immunohistochemical expression and capillary density in pancreatic solid pseudopapillary neoplasm. Ann Diagn Pathol. 2015; 19(2):45-9. DOI: 10.1016/j.anndiagpath.2015.02.002. View

Carstens P, Cressman Jr F . Malignant oncocytic carcinoid of the pancreas. Ultrastruct Pathol. 1989; 13(1):69-75. DOI: 10.3109/01913128909051162. View

Yang M, Zeng L, Zhang Y, Wang W, Wang L, Ke N . TNM staging of pancreatic neuroendocrine tumors: an observational analysis and comparison by both AJCC and ENETS systems from 1 single institution. Medicine (Baltimore). 2015; 94(12):e660. PMC: 4554009. DOI: 10.1097/MD.0000000000000660. View

Ohara Y, Oda T, Hashimoto S, Akashi Y, Miyamoto R, Enomoto T . Pancreatic neuroendocrine tumor and solid-pseudopapillary neoplasm: Key immunohistochemical profiles for differential diagnosis. World J Gastroenterol. 2016; 22(38):8596-8604. PMC: 5064041. DOI: 10.3748/wjg.v22.i38.8596. View

10.

Meriden Z, Shi C, Edil B, Ellison T, Wolfgang C, Cornish T . Hyaline globules in neuroendocrine and solid-pseudopapillary neoplasms of the pancreas: a clue to the diagnosis. Am J Surg Pathol. 2011; 35(7):981-8. PMC: 3283163. DOI: 10.1097/PAS.0b013e31821a9a14. View

11.

Tang L, Basturk O, Sue J, Klimstra D . A Practical Approach to the Classification of WHO Grade 3 (G3) Well-differentiated Neuroendocrine Tumor (WD-NET) and Poorly Differentiated Neuroendocrine Carcinoma (PD-NEC) of the Pancreas. Am J Surg Pathol. 2016; 40(9):1192-202. PMC: 4988129. DOI: 10.1097/PAS.0000000000000662. View

12.

Breslin M, Zhu M, Lan M . NeuroD1/E47 regulates the E-box element of a novel zinc finger transcription factor, IA-1, in developing nervous system. J Biol Chem. 2003; 278(40):38991-7. PMC: 1236987. DOI: 10.1074/jbc.M306795200. View

13.

Burford H, Baloch Z, Liu X, Jhala D, Siegal G, Jhala N . E-cadherin/beta-catenin and CD10: a limited immunohistochemical panel to distinguish pancreatic endocrine neoplasm from solid pseudopapillary neoplasm of the pancreas on endoscopic ultrasound-guided fine-needle aspirates of the pancreas. Am J Clin Pathol. 2009; 132(6):831-9. DOI: 10.1309/AJCPVT8FCLFDTZWI. View

14.

Allred D, Harvey J, Berardo M, Clark G . Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998; 11(2):155-68. View

15.

Murata M, Takahashi H, Yamada M, Song M, Hiratsuka M . A case of mixed adenoneuroendocrine carcinoma of the pancreas: Immunohistochemical analysis for histogenesis. Medicine (Baltimore). 2017; 96(9):e6225. PMC: 5340454. DOI: 10.1097/MD.0000000000006225. View

16.

Fujino K, Motooka Y, Hassan W, Ali Abdalla M, Sato Y, Kudoh S . Insulinoma-Associated Protein 1 Is a Crucial Regulator of Neuroendocrine Differentiation in Lung Cancer. Am J Pathol. 2015; 185(12):3164-77. DOI: 10.1016/j.ajpath.2015.08.018. View

17.

Wang H, Chen Y, Fernandez-Del Castillo C, Yilmaz O, Deshpande V . Heterogeneity in signaling pathways of gastroenteropancreatic neuroendocrine tumors: a critical look at notch signaling pathway. Mod Pathol. 2012; 26(1):139-47. DOI: 10.1038/modpathol.2012.143. View

18.

Kasajima A, Yazdani S, Sasano H . Pathology diagnosis of pancreatic neuroendocrine tumors. J Hepatobiliary Pancreat Sci. 2015; 22(8):586-93. DOI: 10.1002/jhbp.208. View

19.

Ohike N, Kosmahl M, Kloppel G . Mixed acinar-endocrine carcinoma of the pancreas. A clinicopathological study and comparison with acinar-cell carcinoma. Virchows Arch. 2004; 445(3):231-5. DOI: 10.1007/s00428-004-1037-x. View

20.

Yachida S, Zhong Y, Patrascu R, Davis M, Morsberger L, Griffin C . Establishment and characterization of a new cell line, A99, from a primary small cell carcinoma of the pancreas. Pancreas. 2011; 40(6):905-10. PMC: 3180880. DOI: 10.1097/MPA.0b013e3182207a58. View