Nuclear Insulinoma-Associated Protein 1 Expression as a Marker of Neuroendocrine Differentiation in Neoplasms of the Breast

Seijnhaeve, Elsa; Galant, Christine; Bockstal, Mieke Van

doi:10.1177/1066896920985938

Cited by 10 publications

(19 citation statements)

References 27 publications

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“…Of the 22 cases, 5/22 were SYP+/CgA+/INSM1+, 1/22 was SYN+/CgA+/INSM1-, 8/22 were SYN+/CgA-/INSM1+, and 3/22 were SYN-/CgA-/INSM1+, while 5/22 cases were negative for all three markers. Overall, INSM1 was expressed in 16/22 cases, which was higher than those for SYN (14/22) and CgA (6/22) [ 63 ]. INSM1 expression was found in all solid papillary carcinoma cases (5% to 99% nuclear expression), while mucinous carcinomas showed minimal nuclear expression (1% to 5%) [ 63 ].…”

Section: Insm1 Expression In Breast Carcinomas With Neuroendocrine Differentiationmentioning

confidence: 99%

INSM1, a Novel Biomarker for Detection of Neuroendocrine Neoplasms: Cytopathologists’ View

Maleki

Nadella

et al. 2021

Diagnostics

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Background: Insulinoma-associated protein 1 (INSM1) has been considered as a novel immunostain for neuroendocrine tumors (NETs) and is hypothesized to be more reliable than first-generation NET biomarkers, such as CGA (chromogranin A), SYP (synaptophysin) and CD56 (neural cell adhesion molecule). In this review, we summarize existing literature on INSM1′s reliability as an immunostain for detection of various NETs, its results in comparison to first-generation NET biomarkers, and its expression in both non-NETs and benign tissues/cells on cytology specimens (cell blocks/smears).

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Section: Insm1 Expression In Breast Carcinomas With Neuroendocrine Differentiationmentioning

confidence: 99%

INSM1, a Novel Biomarker for Detection of Neuroendocrine Neoplasms: Cytopathologists’ View

Maleki

Nadella

et al. 2021

Diagnostics

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“…In conclusion, consistently with data from other organs, we propose that STX1 is a promising novel, highly sensitive and specific, easily applicable NE marker. Along with INSM1, another recently identified and already better studied (16,18,20) molecule, we strongly recommend STX1 to be included in the routine diagnostic IHC panel of NE differentiation. Following further studies, STX1 and INSM1 may become ancillary markers of SYP and be able to replace the less sensitive CGA and CD56 in the area of breast neoplasia with NE features.…”

Section: Discussionmentioning

confidence: 99%

“…Conceptually, these novel biomolecules may either serve as components of the neurosecretory apparatus, or act as master regulators of NE differentiation. The latter category is represented by INSM1, a transcription factor which is of particular interest and has been a subject of recent studies in various organs (16)(17)(18)(19). An example for the former one is STX1, which has also proved to be a sensitive and specific NE marker (10).…”

Section: Discussionmentioning

confidence: 99%

Syntaxin-1 and Insulinoma-Associated Protein 1 Expression in Breast Neoplasms with Neuroendocrine Features

Turkevi-Nagy¹,

Báthori²,

Böcz³

et al. 2021

Pathol. Oncol. Res.

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Introduction: A subset of breast neoplasia is characterized by features of neuroendocrine differentiation. Positivity for Neuroendocrine markers by immunohistochemistry is required for the diagnosis. Sensitivity and specificity of currently used markers are limited; based on the definitions of WHO Classification of Tumours, 5th edition, about 50% of breast tumors with features of neuroendocrine differentiation express chromogranin-A and 16% express synaptophysin. We assessed the applicability of two novel markers, syntaxin-1 and insulinoma-associated protein 1 (INSM1) in breast carcinomas.Methods: Hypercellular (Type B) mucinous carcinomas, solid papillary carcinomas, invasive carcinomas of no special type with neuroendocrine features and ductal carcinomas in situ of neuroendocrine subtype were included in our study. The immunohistochemical panel included chromogranin A, synaptophysin, CD56, syntaxin-1 and INSM1. The specificity of syntaxin-1 and INSM1 was determined using samples negative for chromogranin A, synaptophysin and CD56.Results: The sensitivity of syntaxin-1 was 84.7% (50/59), with diffuse positivity in more than 60% of the cases. Syntaxin-1 also had an excellent specificity (98.1%). Depending on the definition for positivity, the sensitivity of INSM1 was 89.8% (53/59) or 86.4% (51/59), its specificity being 57.4% or 88.9%. The sensitivities of chromogranin A, synaptophysin and CD56 were 98.3, 74.6 and 22.4%, respectively.Discussion: Syntaxin-1 and INSM1 are sensitive and specific markers of breast tumors with neuroendocrine features, outperforming chromogranin A and CD56. We recommend syntaxin-1 and INSM1 to be included in the routine neuroendocrine immunohistochemical panel.

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“…Its nuclear expression was easily recognizable in small biopsies and cytological specimens with scarce material, contributing to diagnostic accuracy in challenging cases [28,29]. Although extensively studied, to date, only few papers [16][17][18]22] reported INSM1 immunoreactivity in BC. The so far reported cases were selected with different criteria, being described as BC with NE differentiation and, when indicated, they mostly included mucinous, solid papillary, or mixed carcinoma variants, which are not included in the currently proposed WHO categories of breast NEN [3].…”

Section: Discussionmentioning

confidence: 99%

“…The intensity (weak to strong) and the percentage of positive tumor cell nuclei were recorded. The cut off for a positive reaction was set at 5% of tumor cells, as previously reported [ 22 ]. Pancreatic tissue, representing appropriate positive (Langerhans islets) and negative (acinar cells) controls, was included in each IHC run.…”

Section: Methodsmentioning

confidence: 99%

INSM1 Expression in Breast Neoplasms with Neuroedocrine Features

et al. 2021

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According to the 2019 WHO classification of breast tumors, neuroendocrine neoplasms (NENs) are classified into well-differentiated NE tumors (NET) and poorly differentiated NE carcinomas (NEC), while other breast cancers (BCs) of special and no special type with neuroendocrine (NE) features are not incorporated in this scheme anymore. We aimed to assess whether INSM1, a novel NE marker, could have a role in breast NEN subtyping. We selected 63 BCs operated from 2003 to 2018, classified as BCs with NE features, with available clinico-pathological data. Following 2019 WHO criteria, this cohort was reclassified into 37 NETs/NECs, the remaining 26 tumors representing solid-papillary (7), mucinous (7), and mixed type (12) carcinomas with NE differentiation. Chromogranin A (CGA) and synaptophysin (SYN) immunostains were reviewed, and INSM1 was tested by immunohistochemistry. Thirty CGA- and SYN-negative no special type BCs served as negative control. INSM1 was expressed in 52/63 cases of the whole cohort (82.54%). INSM1 positive and negative cases had no significantly different clinico-pathological characteristics. INSM1 expression was not significantly different between the newly reclassified NET/NEC group and other BCs with NE features. No immunoexpression was observed in control BCs. The sensitivity and specificity of INSM1 for the NE phenotype was 82.5% and 100%, respectively, compared to 61.9% and 100% for CGA, and 95.2 and 100% for SYN. In conclusion, INSM1 is as accurate as traditional NE biomarkers to identify NE differentiation in BC. In analogy to standard NE markers, INSM1 could not distinguish NET and NEC from the other BC histotypes with NE differentiation.

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Nuclear Insulinoma-Associated Protein 1 Expression as a Marker of Neuroendocrine Differentiation in Neoplasms of the Breast

Cited by 10 publications

References 27 publications

INSM1, a Novel Biomarker for Detection of Neuroendocrine Neoplasms: Cytopathologists’ View

INSM1, a Novel Biomarker for Detection of Neuroendocrine Neoplasms: Cytopathologists’ View

Syntaxin-1 and Insulinoma-Associated Protein 1 Expression in Breast Neoplasms with Neuroendocrine Features

INSM1 Expression in Breast Neoplasms with Neuroedocrine Features

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