Diagnostic Value of Insulinoma-Associated Protein 1 (INSM1) and Comparison With Established Neuroendocrine Markers in Pulmonary Cancers

Abstract

Context.— The diagnostic distinction of pulmonary neuroendocrine (NE) tumors from non–small cell lung carcinomas (NSCLCs) is clinically relevant for prognostication and treatment. Diagnosis is based on morphology and immunohistochemical staining. Objective.— To determine the diagnostic value of insulinoma-associated protein 1 (INSM1), in comparison with established NE markers, in pulmonary tumors. Design.— Fifty-four pulmonary NE tumors and 632 NSCLCs were stained for INSM1, CD56, chromogranin A, and synaptophysin. In a subset, gene expression data were available for analysis. Also, 419 metastases to the lungs were stained for INSM1. A literature search identified 39 additional studies with data on NE markers in lung cancers from the last 15 years. Seven of these included data on INSM1. Results.— A positive INSM1 staining was seen in 39 of 54 NE tumors (72%) and 6 of 623 NSCLCs (1%). The corresponding numbers were 47 of 54 (87%) and 14 of 626 (2%) for CD56, 30 of 54 (56%) and 6 of 629 (1%) for chromogranin A, and 46 of 54 (85%) and 49 of 630 (8%) for synaptophysin, respectively. Analysis of literature data revealed that CD56 and INSM1 were the best markers for identification of high-grade NE pulmonary tumors when considering both sensitivity and specificity, while synaptophysin also showed good sensitivity. INSM1 gene expression was clearly associated with NE histology. Conclusions.— The solid data of both our and previous studies confirm the diagnostic value of INSM1 as a NE marker in pulmonary pathology. The combination of CD56 with INSM1 and/or synaptophysin should be the first-hand choice to confirm pulmonary high-grade NE tumors. INSM1 gene expression could be used to predict NE tumor histology.

Transcriptomic analysis identifies a tumor subtype mRNA classifier for invasive non-functioning pituitary neuroendocrine tumor diagnostics

“…The second marker INSM1, a zinc finger transcription factor is implicated in the differentiation of endocrine cells in the pituitary and other tissues 51 , and its expression is significantly increased in multiple neuroendocrine neoplasms. Our finding of 100% positive INSM1 immunostaining in NF-PitNEts is in line with the results from the central nervous system neoplasms 52 and neuroendocrine tumors 53 . Recent studies have demonstrated that INSM1 staining outperforms conventional markers for identifying and grading neuroendocrine tumors 40 , 54 , 55 .…”

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

“…The sensitivity and specificity of INSM1 have been extensively studied in neuroendocrine lung neoplasms, and was often found to be superior to the "classic" firstgeneration biomarkers. [18][19][20] Since the evidence regarding INSM1 expression in breast tumors is presently limited to 3 case series and 1 large cohort, 1,2,8,9 we aimed to evaluate this novel biomarker in a series of special type breast carcinomas and invasive carcinomas NST previously diagnosed as presenting with neuroendocrine differentiation, as determined by immunohistochemistry for the first-generation biomarkers synaptophysin and chromogranin.…”

Methylation Patterns and Chromatin Accessibility in Neuroendocrine Lung Cancer

“…Finally, we investigated the potential of our data in addressing the need for more specific and sensitive clinical NE markers [28]. Given the specificity of module 6 genes to neural tissues, we further identified a subset with both regions of open chromatin highly positively correlated to gene expression in the NE cell lines and an associated NE-DMR with significant negative correlation to gene expression in bulk tissue, and thus proposed a set of candidate genes to be investigated for their potential as clinical NE markers ( Supplementary Table S5).…”