Secretagogin, a marker for neuroendocrine cells, is more sensitive and specific in large cell neuroendocrine carcinoma compared with the markers CD56, CgA, Syn and Napsin A

Dong,Yunlong; Li,Yongwen; Liu,Renwang; Li,Ying; Zhang,Hongbing; Liu,Hongyu; Chen,Jun

doi:10.3892/ol.2020.11336

Secretagogin, a marker for neuroendocrine cells, is more sensitive and specific in large cell neuroendocrine carcinoma compared with the markers CD56, CgA, Syn and Napsin A

Authors:
- Yunlong Dong
- Yongwen Li
- Renwang Liu
- Ying Li
- Hongbing Zhang
- Hongyu Liu
- Jun Chen
View Affiliations

Affiliations: Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
Published online on: January 23, 2020 https://doi.org/10.3892/ol.2020.11336
Pages: 2223-2230
Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

A common method to distinguish large cell neuroendocrine carcinoma (LCNEC) from non‑neuroendocrine large cell carcinoma (non‑NE LCC) is from using specific immunohistochemistry markers, such as CgA, Syn, CD56 and Napsin A, however, the results remain controversial using these markers. Secretagogin (SCGN) is a newly discovered biomarker of neuroendocrine cells. In the present study, the expression of SCGN in 33 cases of human lung large cell carcinoma (LCC), including 17 cases of LCNEC and 16 cases of non‑neuroendocrine (NE) LCC and lung cancer cell lines (A549, H1650, H358, H292 and H661). The association between SCGN expression and the clinicopathological characteristics of patients, including sex, age, clinical stage and metastasis, was analyzed. The results revealed that the different lung cancer cell lines had different expression levels of SCGN, and the SCGN protein was localized in the nucleus and cytoplasm of A549 cells detected using immunofluorescence. A total of 54.5% (18/33) of specimens positively expressed the SCGN protein. Of the 17 patients with LCNEC, only 23.5% (4/17) of cases were CgA positive, 35.29% (6/17) were Syn positive, 41.2% (7/17) were CD56 positive, and 41.2% (7/17) were Napsin A positive. However, SCGN was positively detected in 94.1% (16/17) of patients with LCNEC, which was more frequent compared with that in CgA, Syn, CD56 and Napsin A. Analysis of the clinical characteristics indicated that SCGN expression was only significantly associated with pathological type in patients with lung cancer (P<0.001). Furthermore, a positive correlation was observed between SCGN expression and CgA, Syn, and CD56 expression in patients with LCNEC. SCGN was co‑localized with the NE markers (CgA, Syn, and CD56) in A549 lung cancer cells and in LCNEC tissues. Thus, SCGN displayed more sensitivity and specificity in lung cancer cells with NE differentiation. A combined analysis of SCGN and other common NE markers may be a potential tool for diagnosing these tumors.

View Figures

View References

1	Molina JR, Yang P, Cassivi SD, Schild SE and Adjei AA: Non-small cell lung cancer: Epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 83:584–594. 2008. View Article : Google Scholar : PubMed/NCBI
2	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
3	Zhang C, Min L, Zhang L, Ma Y, Yang Y and Shou C: Combined analysis identifies six genes correlated with augmented malignancy from non-small cell to small cell lung cancer. Tumour Biol. 37:2193–2207. 2016. View Article : Google Scholar : PubMed/NCBI
4	Pelosi G, Barbareschi M, Cavazza A, Graziano P, Rossi G and Papotti M: Large cell carcinoma of the lung: A tumor in search of an author. A clinically oriented critical reappraisal. Lung Cancer. 87:226–231. 2015. View Article : Google Scholar : PubMed/NCBI
5	Zheng M: Classification and pathology of lung cancer. Surg Oncol Clin N Am. 25:447–468. 2016. View Article : Google Scholar : PubMed/NCBI
6	Rusch VW, Klimstra DS and Venkatraman ES: Molecular markers help characterize neuroendocrine lung tumors. Ann Thorac Surg. 62:798–810. 1996. View Article : Google Scholar : PubMed/NCBI
7	Hamilton G and Rath B: Smoking, inflammation and small cell lung cancer: Recent developments. Wien Med Wochenschr. 165:379–386. 2015. View Article : Google Scholar : PubMed/NCBI
8	Yamazaki S, Sekine I, Matsuno Y, Takei H, Yamamoto N, Kunitoh H, Ohe Y, Tamura T, Kodama T, Asamura H, et al: Clinical responses of large cell neuroendocrine carcinoma of the lung to cisplatin-based chemotherapy. Lung Cancer. 49:217–223. 2005. View Article : Google Scholar : PubMed/NCBI
9	Liang R, Chen TX, Wang ZQ, Jin KW, Zhang LY, Yan QN, Zhang HH and Wang WP: A retrospective analysis of the clinicopathological characteristics of large cell carcinoma of the lung. Exp Ther Med. 9:197–202. 2015. View Article : Google Scholar : PubMed/NCBI
10	Lai M, Lu B, Xing X, Xu E, Ren G and Huang Q: Secretagogin, a novel neuroendocrine marker, has a distinct expression pattern from chromogranin A. Virchows Arch. 449:402–409. 2006. View Article : Google Scholar : PubMed/NCBI
11	Birkenkamp-Demtroder K, Wagner L, Brandt Sorensen F, Bording Astrup L, Gartner W, Scherubl H, Heine B, Christiansen P and Ørntoft TF: Secretagogin is a novel marker for neuroendocrine differentiation. Neuroendocrinol. 82:121–138. 2005. View Article : Google Scholar
12	Sharma AK, Khandelwal R, Sharma Y and Rajanikanth V: Secretagogin, a hexa EF-hand calcium-binding protein: High level bacterial overexpression, one-step purification and properties. Protein Expr Purif. 109:113–119. 2015. View Article : Google Scholar : PubMed/NCBI
13	Li Y, Li Y, Liu J, Fan Y, Li X, Dong M, Liu H and Chen J: Expression levels of microRNA-145 and microRNA-10b are associated with metastasis in non-small cell lung cancer. Cancer Biol Ther. 17:272–279. 2016. View Article : Google Scholar : PubMed/NCBI
14	Mountain CF: Revisions in the international system for staging lung cancer. Chest. 111:1710–1717. 1997. View Article : Google Scholar : PubMed/NCBI
15	Blumenthal RD, Leon E, Hansen HJ and Goldenberg DM: Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers. BMC Cancer. 7:22007. View Article : Google Scholar : PubMed/NCBI
16	Li Y, Zhang H, Gong H, Yuan Y, Li Y, Wang C, Li W, Zhang Z, Liu M, Liu H and Chen J: miR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin gene. J Exp Clin Cancer Res. 37:1412018. View Article : Google Scholar : PubMed/NCBI
17	Alpár A, Attems J, Mulder J, Hökfelt T and Harkany T: The renaissance of Ca2+-binding proteins in the nervous system: Secretagogin takes center stage. Cell Signal. 24:378–387. 2012. View Article : Google Scholar : PubMed/NCBI
18	Ilhan A, Neziri D, Maj M, Mazal PR, Susani M, Base W, Gartner W and Wagner L: Expression of secretagogin in clear-cell renal cell carcinomas is associated with a high metastasis rate. Hum Pathol. 42:641–648. 2011. View Article : Google Scholar : PubMed/NCBI
19	Attems J, Preusser M, Grosinger-Quass M, Wagner L, Lintner F and Jellinger K: Calcium-binding protein secretagogin-expressing neurones in the human hippocampus are largely resistant to neurodegeneration in Alzheimer's disease. Neuropathol Appl Neurobiol. 34:23–32. 2008.PubMed/NCBI
20	Maj M, Gartner W, Ilhan A, Neziri D, Attems J and Wagner L: Expression of TAU in insulin-secreting cells and its interaction with the calcium-binding protein secretagogin. J Endocrinol. 205:25–36. 2010. View Article : Google Scholar : PubMed/NCBI
21	Wang YH, Yang QC, Lin Y, Xue L, Chen MH and Chen J: Chromogranin A as a marker for diagnosis, treatment and survival in patients with gastroenteropancreatic neuroendocrine neoplasm. Medicine (Baltimore). 93:e2472014. View Article : Google Scholar : PubMed/NCBI
22	Takeuchi T, Minami Y, Iijima T, Kameya T, Asamura H and Noguchi M: Characteristics of loss of heterozygosity in large cell neuroendocrine carcinomas of the lung and small cell lung carcinomas. Pathol Int. 56:434–439. 2006. View Article : Google Scholar : PubMed/NCBI
23	Wiedenmann B, Franke WW, Kuhn C, Moll R and Gould VE: Synaptophysin: A marker protein for neuroendocrine cells and neoplasms. Proc Natl Acad Sci USA. 83:3500–3504. 1986. View Article : Google Scholar : PubMed/NCBI
24	Farinola MA, Weir EG and Ali SZ: CD56 expression of neuroendocrine neoplasms on immunophenotyping by flow cytometry: A novel diagnostic approach to fine-needle aspiration biopsy. Cancer. 99:240–246. 2003. View Article : Google Scholar : PubMed/NCBI
25	Turner BM, Cagle PT, Sainz IM, Fukuoka J, Shen SS and Jagirdar J: Napsin A, a new marker for lung adenocarcinoma, is complementary and more sensitive and specific than thyroid transcription factor 1 in the differential diagnosis of primary pulmonary carcinoma: Evaluation of 1674 cases by tissue microarray. Arch Pathol Lab Med. 136:163–171. 2012. View Article : Google Scholar : PubMed/NCBI
26	Loy TS, Darkow GV and Quesenberry JT: Immunostaining in the diagnosis of pulmonary neuroendocrine carcinomas. An immunohistochemical study with ultrastructural correlations. Am J Surg Pathol. 19:173–182. 1995. View Article : Google Scholar : PubMed/NCBI