Ömer ÖNAL, Cevat YAZICI, Olgun KONTAŞ, Fahrettin KELEŞTEMUR, Nuri TUTAR, Nur Aleyna YETKİN

Clinical significance of progastrin-releasing peptide, neuron-specific enolase, chromogranin a, and squamous cell cancer antigen in pulmonary neuroendocrine tumors

Background/aim: It is not always easy to diagnose pulmonary neuroendocrine tumors (PNETs). The aim of the present study is to makea differential diagnosis by studying the same markers in patients with non-small-cell lung carcinoma (NSCLC), patients with benignlung disease (chronic obstructive pulmonary disease and pneumonia), and healthy volunteers to determine the roles of these markersin pulmonary neuroendocrine tumor diagnosis and to identify their power.Materials and methods: A total of 100 participants including 23 PNET patients and 28 NSCLC patients who were pathologically diagnosed but not yet treated, 25 participants with benign disease, and 24 healthy volunteers were included in this cross-sectional study.Results: No significant difference was found between the chromogranin A (CgA) and squamous cell carcinoma antigen 1 (SCCA1)values among the groups (PNET, NSCLC, benign, healthy volunteers), but the difference in progesterone-releasing peptide (ProGRP),neuron-specific enolase (NSE), and adjusted NSE was statistically significant (P values were respectively ProGRP, P = 0.006; NSE, P =0.015; NSE adjusted, P = 0.09). In a comparison of the PNET and NSCLC groups, having a ProGRP value higher than 84.6 pg/mL revealed PNET with 60.9% sensitivity and 89.3% specificity (P = 0.001).Conclusion: The ProGRP value is the only indicator that distinguishes the PNET group from the other 3 groups.

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1. Govindan R, Page N, Morgensztern D, Read W, Tierney R et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. Journal of Clinical Oncology 2006; 24 (28): 4539-4544.
2. Kalemkerian GP, Akerley W, Bogner P, Borghaei H, Chow LQ et al. Small cell lung cancer. Journal of the National Comprehensive Cancer Network 2013; 11 (1): 78-98.
3. Öberg K, Hellman P, Kwekkeboom D, Jelic S; ESMO Guidelines Working Group. Neuroendocrine bronchial and thymic tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 2010; 21 (Suppl. 5): v220-v222.
4. Caplin ME, Baudin E, Ferolla P, Filosso P, Garcia-Yuste M et al. Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids. Annals of Oncology 2015; 26 (8): 1604-1620.
5. Detterbeck FC. Management of carcinoid tumors. Annals of Thoracic Surgery 2010; 89 (3): 998-1005.
6. Gustafsson BI, Kidd M, Chan A, Malfertheiner MV, Modlin IM. Bronchopulmonary neuroendocrine tumors. Cancer 2008; 113 (1): 5-21.
7. Soga J, Yakuwa Y. Bronchopulmonary carcinoids: an analysis of 1,875 reported cases with special reference to a comparison between typical carcinoids and atypical varieties. Annals of Thoracic and Cardiovascular Surgery 1999; 5 (4): 211-219.
8. Travis W. Advances in neuroendocrine lung tumors. Annals of Oncology 2010; 21 (Suppl. 7): vii65-vii71.
9. Lamy PJ, Grenier J, Kramar A, Pujol JL. Pro-gastrin-releasing peptide, neuron specific enolase and chromogranin A as serum markers of small cell lung cancer. Lung Cancer 2000; 29 (3): 197-203.
10. Molina R, Auge JM, Alicarte J, Filella X, Viñolas N et al. Progastrin-releasing peptide in patients with benign and malignant diseases. Tumor Biology 2004; 25 (1-2): 56-61.
11. Nisman B, Biran H, Ramu N, Heching N, Barak V et al. The diagnostic and prognostic value of ProGRP in lung cancer. Anticancer Research 2009; 29 (11): 4827-4832.
12. Okusaka T, Eguchi K, Kasai T, Kurata T, Yamamoto N et al. Serum levels of pro-gastrin-releasing peptide for follow-up of patients with small cell lung cancer. Clinical Cancer Research 1997; 3 (1): 123-127.
13. Stieber P, Dienemann H, Schalhorn A, Schmitt U, Reinmiedl J et al. Pro-gastrin-releasing peptide (ProGRP): a useful marker in small cell lung carcinomas. Anticancer Research 1998; 19 (4A): 2673-2678.
14. Takada M, Kusunoki Y, Masuda N, Matui K, Yana T et al. Progastrin-releasing peptide (31-98) as a tumour marker of smallcell lung cancer: comparative evaluation with neuron-specific enolase. British Journal of Cancer 1996; 73 (10): 1227.
15. Goto K, Kodama T, Hojo F, Kubota K, Kakinuma R et al. Clinicopathologic characteristics of patients with nonsmall cell lung carcinoma with elevated serum progastrin-releasing peptide levels. Cancer 1998; 82 (6): 1056-1061.
16. Harmsma M, Schutte B, Ramaekers FC. Serum markers in small cell lung cancer: opportunities for improvement. Biochimica et Biophysica Acta Reviews on Cancer 2013; 1836 (2): 255-272.
17. Jørgensen L, Osterlind K, Genolla J, Gomm S, Hernandez J et al. Serum neuron-specific enolase (S-NSE) and the prognosis in small-cell lung cancer (SCLC): a combined multivariable analysis on data from nine centres. British Journal of Cancer 1996; 74 (3): 463.
18. Rapellino M, Pecchio F, Cunazza M, Baldi S, Adamo M et al. Determination of serum neuron-specific enolase in bronchial tumors of neuroendocrine origin. Minerva Medica 1988; 79 (12): 1051-1052.
19. Seregni E, Ferrari L, Bajetta E, Martinetti A, Bombardieri E. Clinical significance of blood chromogranin A measurement in neuroendocrine tumours. Annals of Oncology 2001; 12 (Suppl. 2): S69-S72.
20. Taneja TK, Sharma S. Markers of small cell lung cancer. World Journal of Surgical Oncology 2004; 2 (1): 10.
21. Kagohashi K, Satoh H, Kurishima K, Kadono K, Ishikawa H et al. Squamous cell carcinoma antigen in lung cancer and nonmalignant respiratory diseases. Lung 2008; 186 (5): 323-326.
22. Molina R, Augé JM, Bosch X, Escudero JM, Viñolas N et al. Usefulness of serum tumor markers, including progastrin-releasing peptide, in patients with lung cancer: correlation with histology. Tumor Biology 2009; 30 (3): 121-129.
23. Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H et al. The IASLC Lung Cancer Staging Project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. Journal of Thoracic Oncology 2016; 11 (1): 39-51.
24. Stahel RA, Ginsberg R, Havemann K, Hirsch FR, Ihde DC et al. Staging and prognostic factors in small cell lung cancer: a consensus report. Lung Cancer 1989; 5 (4-6): 119-126.
25. Verfaillie CJ, Delanghe JR. Hemolysis correction factor in the measurement of serum neuron-specific enolase. Clinical Chemistry and Laboratory Medicine 2010; 48 (6): 891-892.
26. Goksuluk D, Korkmaz S, Zararsiz G, Karaagaoglu AE. easyROC: an interactive web-tool for ROC curve analysis using R language environment. The R Journal 2016; 8: 213-230.
27. Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd ed. Hillsdale, NJ, USA: Erlbaum Associates; 1988.
28. Korse CM, Taal BG, Bonfrer JM, Vincent A, Van Velthuysen M et al. An elevated progastrin-releasing peptide level in patients with well-differentiated neuroendocrine tumours indicates a primary tumour in the lung and predicts a shorter survival. Annals of Oncology 2011; 22 (12): 2625-2630.
29. Shibayama T, Ueoka H, Nishii K, Kiura K, Tabata M et al. Complementary roles of progastrin-releasing peptide (ProGRP) and neuron specific enolase (NSE) in diagnosis and prognosis of small-cell lung cancer (SCLC). Lung Cancer 2001; 32 (1): 61-69.
30. Tolan NV, Vidal-Folch N, Algeciras-Schimnich A, Singh RJ, Grebe SK. Individualized correction of neuron-specific enolase (NSE) measurement in hemolyzed serum samples. Clinica Chimica Acta 2013; 424: 216-221.
31. Nobels FR, Kwekkeboom DJ, Coopmans W, Schoenmakers CH, Lindemans J et al. Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the α-subunit of glycoprotein hormones. Journal of Clinical Endocrinology & Metabolism 1997; 82 (8): 2622- 2628.
32. Børglum T, Rehfeld JF, Drivsholm LB, Hilsted L. Processingindependent quantitation of chromogranin A in plasma from patients with neuroendocrine tumors and small-cell lung carcinomas. Clinical Chemistry 2007; 53 (3): 438-446.