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.
invasion (p¼0.0335), and expression of MMP2 (0.0081), were observed, although S100A10 expression was not an independent predictor of a poorer survival in the multivariable analysis (HR 1.7334, 95%CI 0.4340-11.523, p¼0.4647). In the same way, 33 (27.5%) of 120 SCCs showed S100A10-positive staining and correlation with poorer prognosis (p¼0.0094), p-TNM stage (p¼0.0119), nodal involvement (p¼0.0006), lymphatic invasion (p¼0.0005), and tumor size (p¼0.0003) were observed. As for lung SCCs, S100A10 expression was an independent predictor of a poorer survival in the multivariable analysis (HR 9.5916, 95%CI 1.0702-128.208, p¼0.0434). Then we performed knockdown of S100A10 in lung cancer cell lines and found that knockdown of S100A10 suppressed cell proliferation in adenocarcinomas and SCCs, and invasion in adenocarcinomas. Conclusion: In this study, we found that S100A10 expression associates with poorer survival in lung SCCs, but not in lung adenocarcinoma. Our present results suggest that S100A10 protein plays an important role in proliferation of lung cancer, possibly in association with invasion by MMPs. Future studies are necessary to further understanding of importance of S100A10 in progression of human lung cancer, including some differences between histological subtypes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.