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Utility of secretagogin as a marker for the diagnosis of lung neuroendocrine carcinoma

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Abstract

Small-cell lung cancers (SCLC) and large-cell neuroendocrine carcinomas (LCNEC) are two types of high-grade pulmonary neuroendocrine carcinomas (NECs). Diagnostic neuroendocrine markers commonly include synaptophysin, chromogranin A, CD56, and insulinoma-associated protein 1 (INSM1). In this study, the utility of secretagogin (SCGN) was examined in the context of pulmonary NEC diagnosis. The study included 71 pulmonary NEC cases (18 SCLCs, 13 combined-SCLCs, 23 LCNECs, and 17 combined-LCNECs). Immunohistochemical stains of SCGN, synaptophysin, chromogranin A, CD56, and INSM1 were performed on whole tumor sections. The stains were evaluated based on combined staining intensity and the proportion of positive tumor cells. At least mild staining intensity in at least 1% of the cells was considered positive. Bioinformatic studies showed specific SCGN expression in neuroendocrine cells and NECs. SCGN showed diffuse nuclear and cytoplasmic staining in NECs with intra-tumoral heterogeneity. The non-neuroendocrine components were negative. The sensitivity of SCGN was no better than the other established neuroendocrine markers based on all NECs combined or LCNECs/c-LCNECs only. However, the sensitivity of SCGN (71%) was higher than chromogranin A (68%) for SCLCs/c-SCLCs only. The average proportion of SCGN positive tumor cells was 8% higher than chromogranin A (22% versus 14%, P = 0.0332) in all NECs and 18% higher for SCLC and c-SCLC cases only (32% versus 13%, P = 0.0054). The above data showed that SCGN could be used as a supplemental neuroendocrine marker to diagnose SCLC.

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Funding

This study was supported by Department of Pathology and Laboratory Medicine of Lifespan Academic Center.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Alpert Medical School of Brown University, Providence, RI, 02903, USA

    Yigit Baykara, Ying Xiao, Dongfang Yang, Evgeny Yakirevich, Sara Maleki, Maria Garcia-Moliner, Li Juan Wang & Shaolei Lu

  2. Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, 70112, USA

    Chiung-Kuei Huang

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  1. Yigit Baykara
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  2. Ying Xiao
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  7. Li Juan Wang
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  9. Shaolei Lu
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Contributions

SL and YB contributed to the study conception and design. Material preparation, data collection, and analysis were performed by YB, YX, DY, and SL. YB performed IHC scoring, and the consensus was reached between YB and SL when necessary. The first draft of the manuscript was written by YB and SL. EY, MGM, SM, LJW, and CKH commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Shaolei Lu.

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The study was approved by the Internal Review Board of Rhode Island Hospital and The Miram Hospital.

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The study did not involve human participants or animals.

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Baykara, Y., Xiao, Y., Yang, D. et al. Utility of secretagogin as a marker for the diagnosis of lung neuroendocrine carcinoma. Virchows Arch 481, 31–39 (2022). https://doi.org/10.1007/s00428-022-03312-9

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  • DOI: https://doi.org/10.1007/s00428-022-03312-9

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