Insulinoma-associated protein 1 (INSM1) is a useful marker for pancreatic neuroendocrine tumor

Tanigawa, Masahiko; Nakayama, Masamichi; Taira, Tomoki; Hattori, Satoshi; Mihara, Yutaro; Kondo, Reiichiro; Kusano, Hironori; Nakamura, Ken; Abe, Yushi; Ishida, Yusuke; Okabe, Yoshinobu; Hisaka, Toru; Okuda, K; Fujita, Kosuke; Ito, Takaaki; Kawahara, Akihiko; Naito, Yoshiki; Yamaguchi, Rin; Akiba, Jun; Akagi, Yoshito; Yano, Hirohisa

doi:10.1007/s00795-017-0167-6

Cited by 83 publications

(81 citation statements)

References 19 publications

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“…To further evaluate the specificity of SYN, CgA, and INSM1, we analysed their expression in primary pancreatic acinar cell carcinoma and solid pseudopapillary neoplasm, which can histologically mimic GEP‐NEN. A prior study evaluating INSM1 expression in seven and four cases of acinar cell carcinoma and solid pseudopapillary neoplasm, respectively, had revealed none of those cases to be positive . In our cohort, INSM1 was expressed in one of the nine (11%) cases of solid pseudopapillary neoplasm, with 90% of the tumour cells being reactive.…”

Section: Discussionsupporting

confidence: 38%

Insulinoma‐associated protein 1 expression in primary and metastatic neuroendocrine neoplasms of the gastrointestinal and pancreaticobiliary tracts

González

Sninsky

et al. 2019

Histopathology

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Aims Insulinoma‐associated protein 1 (INSM1) is a transcription factor that is expressed in developing and mature neuroendocrine tissue. Recent studies have shown that INSM1 is a sensitive marker for neuroendocrine tumours. The aims of this study were to evaluate INSM1 expression in primary gastroenteropancreatic neuroendocrine neoplasms (GEP‐NENs) and in their known metastases, in order to assess its sensitivity as compared with chromogranin‐A (CgA) and synaptophysin (SYN), and to evaluate any change in expression between primary and metastatic disease. Methods and results We identified 30 patients with primary GEP‐NEN. Liver metastatic tissue was available for 26 patients; two patients had two metachronous metastatic foci, yielding a total of 28 metastatic cases. An additional two and seven non‐paired cases of primary and metastatic grade 3 GEP‐NEN, respectively, were included. To assess specificity, we evaluated the expression of these markers in other primary tumours (colorectal adenocarcinoma, acinar cell carcinoma, solid pseudopapillary neoplasm, cholangiocarcinoma, and hepatocellular carcinoma) and metastatic tumours in the liver (adrenal cortical, breast and prostate carcinomas) that may present as differential diagnoses. In our cohort, all of the primary GEP‐NENs and 94% of the metastatic GEP‐NENs expressed INSM1. INSM1 showed similar sensitivity to SYN and higher sensitivity than CgA in both primary and metastatic neoplasms. INSM1 has comparable specificity to CgA, and higher specificity than SYN. Conclusions The nuclear reactivity and the high sensitivity and specificity of INSM1 make it a preferred neuroendocrine marker. In conclusion, INSM1 can be used as a single first‐line marker for primary and metastatic GEP‐NEN.

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Section: Discussionsupporting

confidence: 38%

Insulinoma‐associated protein 1 expression in primary and metastatic neuroendocrine neoplasms of the gastrointestinal and pancreaticobiliary tracts

González

Sninsky

et al. 2019

Histopathology

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“…For NET versus NEC, chromogranin A stains NEC less uniformly and less frequently compared with NET. Insulinoma‐associated protein 1 (INSM1) is a specific nuclear marker for neuroendocrine differentiation, but it does not distinguish well versus poor differentiation . Ki‐67 proliferation should not be relied upon exclusively to discriminate NET from NEC.…”

Section: Differentiation: Cytomorphology and The Use Of Immunohistochmentioning

confidence: 98%

“…Patterns of immunohistochemical staining can aid in the diagnosis of neuroendocrine neoplasms and the distinction between NET, NEC, and other neoplasms with neuroendocrine differentiation. Synaptophysin and chromogranin A typically are strong and diffuse in extra‐adrenal paraganglioma and NET, even in grade 3 NET . Pan‐cytokeratin labeling is helpful for the differential diagnosis of NET and extra‐adrenal paraganglioma, which is negative.…”

Section: Differentiation: Cytomorphology and The Use Of Immunohistochmentioning

confidence: 99%

“…Positive staining for ISL1 in TTF1‐negative/CDX2‐negative NETs supports a pancreatic or rectal origin with a positive predictive value of 100% . Markers with limited or no utility for indicating primary site include CK7, CK20, INSM1, pancreatic and duodenal homeobox 1 (PDX1), and NKX2.2 . Paired box 8 (PAX8) also has limited utility for liver metastasis, because various clones stain NETs from a wide range of sites above and below the diaphragm .…”

Section: Approach To Metastasismentioning

confidence: 99%

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Advances in the cytologic diagnosis of gastroenteropancreatic neuroendocrine neoplasms

Sigel

2018

Cancer Cytopathology

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Two‐thirds of neuroendocrine neoplasms arising in the human body originate from the gastrointestinal system or pancreas. Gastroenteropancreatic neuroendocrine neoplasms are heterogeneous, comprising both well differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The clinical presentation, molecular characteristics, and behavior are distinct for NETs and NECs. Fine‐needle aspiration is an important modality for the primary diagnosis and staging of these neoplasms and can provide information of prognostic and therapeutic significance. Our evolving understanding of neuroendocrine neoplasm biology has led to several iterations of classification. In this review, new concepts and issues most relevant to cytology diagnosis of gastroenteropancreatic neuroendocrine neoplasms are discussed, such as newer detection methods that aid in diagnosis and staging, recent changes in World Health Organization classification, practical issues related to grading these neoplasms on cytology, guidelines for diagnostic reporting, and panels of immunohistochemical stains for the diagnosis of metastasis. The current understanding of genetic and epigenetic events related to tumor development and potential applications for cytology also are presented as they relate to prognostication and recent therapeutic advances.

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“…Increased gene expression was initially demonstrated in SCLC and later in other NE neoplasms, including pheochromocytomas, medullary thyroid carcinomas, medulloblastomas, and pituitary adenomas . INSM1 protein has been found to be expressed consistently in NE and neuroepithelial neoplasms, irrespective of tumor grade, including small cell carcinomas of various sites, and has been proposed as a single marker with high specificity and sensitivity for the diagnosis of SCLC …”

Section: Introductionmentioning

confidence: 99%

Insulinoma‐associated protein 1 is a robust nuclear immunostain for the diagnosis of small cell lung carcinoma in cytology smears

Nakra

Nambirajan

Guleria

et al. 2019

Cancer Cytopathology

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Background In a significant percentage of patients with small cell lung carcinoma (SCLC), cytology samples represent the only source of tumor tissue. Ancillary immunocytochemistry (ICC) for neuroendocrine markers is an important adjunct for the diagnosis of SCLC. Insulinoma‐associated protein 1 (INSM1) is a novel neuroendocrine marker proposed as an economical single‐marker alternative to the traditional 3‐marker panel of chromogranin, synaptophysin, and CD56. To the authors’ knowledge, limited studies have evaluated INSM1 immunohistochemistry (IHC) for the diagnosis of SCLC and reported high sensitivities and specificities. The objective of the current study was to evaluate the sensitivity and specificity of INSM1 ICC on direct smears (DS) from patients with SCLC in comparison with IHC on small biopsies (SBs). Methods All available DS and SBs from patients with SCLC who were diagnosed over the previous year were retrieved. Immunostaining for INSM1 was performed on alcohol‐fixed DS and formalin‐fixed SBs wherever available. A total of 10 DS and SBs from patients with non–small cell lung carcinoma were included for comparison. Nuclear staining for INSM1 in ≥1% tumor cells was interpreted as positive. Results Among a total of 60 patients with SCLC who were included in the current study, a total of 37 underwent INSM1 IHC on SBs and 36 underwent INSM1 ICC on DS. ICC was noninterpretable in 3 DS due to necrosis. The sensitivity of INSM1 IHC was 97% (36 of 37 cases) whereas the sensitivity of INSM1 ICC was 91% (30 of 33 cases) for the diagnosis of SCLC. Among matched IHC and ICC results available for 11 patients, 91% of cases (10 of 11 patients) demonstrated concordant IHC‐ICC staining. All cases of non–small cell lung carcinoma were negative for INSM1 (100% specificity). Conclusions INSM1 appears to be a robust and reliable ICC marker for the confirmation of SCLC diagnosis on cytology smears.

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Insulinoma-associated protein 1 (INSM1) is a useful marker for pancreatic neuroendocrine tumor

Cited by 83 publications

References 19 publications

Insulinoma‐associated protein 1 expression in primary and metastatic neuroendocrine neoplasms of the gastrointestinal and pancreaticobiliary tracts

Insulinoma‐associated protein 1 expression in primary and metastatic neuroendocrine neoplasms of the gastrointestinal and pancreaticobiliary tracts

Advances in the cytologic diagnosis of gastroenteropancreatic neuroendocrine neoplasms

Insulinoma‐associated protein 1 is a robust nuclear immunostain for the diagnosis of small cell lung carcinoma in cytology smears

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