DOI QR코드

DOI QR Code

Preliminary Evaluation of Clinical Utility of CYFRA 21-1, CA 72-4, NSE, CA19-9 and CEA in Stomach Cancer

  • Gwak, Hee Keun (Department of Radiation Oncology, Dankook University College of Medicine) ;
  • Lee, Jai Hyuen (Department of Nuclear Medicine, Dankook University College of Medicine) ;
  • Park, Seok Gun (Department of Nuclear Medicine, Dankook University College of Medicine)
  • Published : 2014.06.30

Abstract

Background: Although various tumor markers have been utilized in management of stomach cancer (SC), only a few reports have described relevance of examples such as CYFRA 21-1 and neuron-specific enolase (NSE). The purpose of this study was to evaluate the potential diagnostic performance of carcinoembryonic antigen (CEA), CA 19-9, CA72-4, CYFRA 21-1 and NSE in patients with SC. Materials and Methods: Ninety-six SC patients with pathologic confirmation between 2012 and 2013 were enrolled. Serum levels of five tumor markers were analyzed using a solid-phase immunoradiometric assay. Receiver operating characteristic (ROC) curves were plotted for the five tumor markers to investigate their diagnostic powers and adjusted cutoff values derived from analysis of ROC curves were evaluated to calculate the sensitivity of each for SC with recommended cutoff values. Results: Based on two different cutoff values (recommended and adjusted), CYFRA 21-1 (${\geq}2.0$ and 1.2 ng/ml) had a respective sensitivity of 50% and 78.1%, compared with 8.3% and 18.8% for CEA (${\geq}7.0$ and 3.9 ng/ml), 15.6% and 18.8% for CA 19-9 (${\geq}37$ and 26.7 ng/ml), 28.1% and 9.6% for CA 72-4 (${\geq}4.0$ and 13 ng/ml) and 7.3% and 7.3% for NSE (${\geq}14.7$ and 15.0 ng/ml) in the initial staging of primary SC. The area under the curve (AUC) for CYFRA 21-1, with a value of 0.978 (95% confidence interval, 0.964-0.991) was comparatively the highest. Univariate analysis revealed significant relationships between tumor marker level and lymph node involvement, metastasis and staging with CYFRA 21-1, CA 72-4 and NSE. Conclusions: CYFRA 21-1 was the most sensitive tumor marker and showed the most powerful diagnostic performance among the five SC tumor markers. NSE and CA 72-4 are significantly related to lymph node involvement, metastasis or stage. Further evaluations are warranted to clarify the clinical usefulness and prognostic prediction of these markers in SC.

Acknowledgement

Supported by : Dankook University

References

  1. Zhang HQ, Wang RB, Yan HJ, et al (2012). Prognostic significance of CYFRA21-1, CEA and hemoglobin in patients with esophageal squamous cancer undergoing concurrent chemoradiotherapy. Asian Pac J Cancer Prev, 13, 199-203. https://doi.org/10.7314/APJCP.2012.13.1.199
  2. Zhu SJ, Zhang Y, Yu YH, et al (2013). FDG PET-CT in non-small cell lung cancer: relationship between primary tumor fdg uptake and extensional or metastatic potential. Asian Pac J Cancer Prev, 14, 2925-29. https://doi.org/10.7314/APJCP.2013.14.5.2925
  3. Sisik A, Kaya M, Bas G, Basak F, Alimoglu O (2013). CEA and CA 19-9 are still valuable markers for the prognosis of colorectal and gastric cancer patients. Asian Pac J Cancer Prev, 14, 4289-94. https://doi.org/10.7314/APJCP.2013.14.7.4289
  4. Nakata B, Takashima T, Ogawa Y, Ishikawa T, Hirakawa K (2004). Serum CYFRA 21-1 (cytokeratin-19 fragments) is a useful tumour marker for detecting disease relapse and assessing treatment efficacy in breast cancer. Br J Cancer, 91, 873-8. https://doi.org/10.1038/sj.bjc.6602074
  5. Qin H, Qu LL, Liu H, Wang SS, Gao HJ (2013). Serum CEA level change and its significance before and after gefitinib therapy on patients with advanced non-small cell lung cancer. Asian Pac J Cancer Prev, 14, 4205-8. https://doi.org/10.7314/APJCP.2013.14.7.4205
  6. Siegel R, Naishadham D, Jemal A (2013). Cancer statistics, 2013. CA: A Cancer J Clin, 63, 11-30. https://doi.org/10.3322/caac.21166
  7. Ubukata H, Katano M, Motohashi G, et al (2003). Evaluation of CA72-4 as a tumor marker in patients with gastric cancer. Gan To Kagaku Ryoho, 30, 1821-4.
  8. Ucar E, Semerci E, Ustun H, et al (2008). Prognostic value of preoperative CEA, CA 19-9, CA 72-4, and AFP levels in gastric cancer. Adv Ther, 25, 1075-84. https://doi.org/10.1007/s12325-008-0100-4
  9. Waldum HL, Aase S, Kvetnoi I, et al (1998). Neuroendocrine differentiation in human gastric carcinoma. Cancer, 83, 435-44. https://doi.org/10.1002/(SICI)1097-0142(19980801)83:3<435::AID-CNCR11>3.0.CO;2-X
  10. Wieskopf B, Demangeat C, Purohit A, et al (1995). Cyfra 21-1 as a biologic marker of non-small cell lung cancer. Evaluation of sensitivity, specificity, and prognostic role. Chest, 108, 163-9. https://doi.org/10.1378/chest.108.1.163
  11. Yoshioka T, Yamaguchi K, Kubota K, et al (2003). Evaluation of 18F-FDG PET in patients with advanced, metastatic, or recurrent gastric cancer. J Nucl Med, 44, 690-9.
  12. Zeltzer PM, Marangos PJ, Evans AE, Schneider SL (1986). Serum neuron-specific enolase in children with neuroblastoma. Relationship to stage and disease course. Cancer, 57, 1230-4. https://doi.org/10.1002/1097-0142(19860315)57:6<1230::AID-CNCR2820570628>3.0.CO;2-#
  13. Lee IK, Kim DH, Gorden DL, et al (2009). Prognostic value of CEA and CA 19-9 tumor markers combined with cytology from peritoneal fluid in colorectal cancer. Ann Surg Oncol, 16, 861-70. https://doi.org/10.1245/s10434-008-0294-3
  14. Koenig A, Wojcieszyn J, Weeks BR, Modiano JF (2001). Expression of S100a, vimentin, NSE, and melan A/MART-1 in seven canine melanoma cells lines and twenty-nine retrospective cases of canine melanoma. Vet Pathol, 38, 427-35. https://doi.org/10.1354/vp.38-4-427
  15. Koga T, Kano T, Souda K, Oka N, Inokuchi K(1987). The clinical usefulness of preoperative CEA determination in gastric cancer. Jpn J Surg, 17, 342-7. https://doi.org/10.1007/BF02470632
  16. Koprowski H, Herlyn M, Steplewski Z, Sears HF (1981). Specific antigen in serum of patients with colon carcinoma. Science, 212, 53-5. https://doi.org/10.1126/science.6163212
  17. Lee JH (2013). Clinical usefulness of serum CYFRA 21-1 in patients with colorectal cancer. Nucl Med Mol Imaging, 47, 181-7. https://doi.org/10.1007/s13139-013-0218-4
  18. Liu X, Cai H, Wang Y (2012). Prognostic significance of tumor markers in T4a gastric cancer. World J Surg Oncol, 10, 1-9. https://doi.org/10.1186/1477-7819-10-1
  19. Mattar R, Andrade CR, DiFavero GM, Gama-Rodrigues JJ, Laudanna AA (2002). Preoperative serum levels of CA 72-4, CEA, CA 19-9, and alpha-fetoprotein in patients with gastric cancer. Rev Hosp Clin Fac Med Sao Paulo, 57, 89-92. https://doi.org/10.1590/S0041-87812002000300001
  20. Moertel CG, O'Fallon JR, Go VL, O'Connell MJ, Thynne GS (1986). The preoperative carcinoembryonic antigen test in the diagnosis, staging, and prognosis of colorectal cancer. Cancer, 58, 603-10. https://doi.org/10.1002/1097-0142(19860801)58:3<603::AID-CNCR2820580302>3.0.CO;2-K
  21. Molina R, Filella X, Auge JM, et al (2003). Tumor markers (CEA, CA 125, CYFRA 21-1, SCC and NSE) in patients with non-small cell lung cancer as an aid in histological diagnosis and prognosis. Comparison with the main clinical and pathological prognostic factors. Tumour Biol, 24, 209-18. https://doi.org/10.1159/000074432
  22. Gaarenstroom KN, Bonfrer JM, Kenter GG, et al (1995). Clinical value of pretreatment serum Cyfra 21-1, tissue polypeptide antigen, and squamous cell carcinoma antigen levels in patients with cervical cancer. Cancer, 76, 807-13. https://doi.org/10.1002/1097-0142(19950901)76:5<807::AID-CNCR2820760515>3.0.CO;2-M
  23. Chen XJ, Li N, Huang YD, et al (2014). Factors for postoperative gallstone occurrence in patients with gastric cancer: a metaanalysis. Asian Pac J Cancer Prev, 15, 877-81. https://doi.org/10.7314/APJCP.2014.15.2.877
  24. Choi AR, Park JC, Kim J, et al (2013). High level of preoperative carbohydrate antigen 19-9 is a poor survival predictor in gastric cancer. World J Gastroenterol, 19, 5302-8. https://doi.org/10.3748/wjg.v19.i32.5302
  25. Duraker N, Celik AN (2001). The prognostic significance of preoperative serum CA 19-9 in patients with resectable gastric carcinoma: comparison with CEA. J Surg Oncol, 76, 266-71. https://doi.org/10.1002/jso.1044
  26. Gartner U, Scheulen ME, Conradt C, et al (1998). Value of tumor-associated antigens CA 72-4 vs CEA and CA 19-9 in the follow-up after stomach cancer. Dtsch Med Wochenschr, 123, 69-73. https://doi.org/10.1055/s-2007-1023900
  27. Ikeguchi M, Katano K, Saitou H, et al (1997). Pre-operative serum levels of CA72-4 in patients with gastric adenocarcinoma. Hepatogastroenterology, 44, 866-71.
  28. Japanese Gastric Cancer Association (2011). Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer, 14, 101-12. https://doi.org/10.1007/s10120-011-0041-5
  29. Jung KW, Won YJ, Kong HJ, et al (2013). Cancer statistics in Korea: incidence, mortality, survival and prevalence in 2010. Cancer Res and Treat, 45,1-14. https://doi.org/10.4143/crt.2013.45.1.1
  30. Kodama I, Koufuji K, Kawabata S, et al (1995). The clinical efficacy of CA 72-4 as serum marker for gastric cancer in comparison with CA19-9 and CEA. Int Surg, 80, 45-8.
  31. Kodera Y, Yamamura Y, Torii A, et al (1996). The prognostic value of preoperative serum levels of CEA and CA19-9 in patients with gastric cancer. Am J Gastroenterol, 91, 49-53.

Cited by

  1. Combined Detection of CEA, CA 19-9, CA 242 and CA 50 in the Diagnosis and Prognosis of Resectable Gastric Cancer vol.15, pp.15, 2014, https://doi.org/10.7314/APJCP.2014.15.15.6295
  2. Prediction of Lung Cancer Based on Serum Biomarkers by Gene Expression Programming Methods vol.15, pp.21, 2014, https://doi.org/10.7314/APJCP.2014.15.21.9367
  3. Tumor Markers for Diagnosis, Monitoring of Recurrence and Prognosis in Patients with Upper Gastrointestinal Tract Cancer vol.15, pp.23, 2015, https://doi.org/10.7314/APJCP.2014.15.23.10267
  4. Value of Combined Detection of Serum CEA, CA72-4, CA19-9 and TSGF in the Diagnosis of Gastric Cancer vol.16, pp.9, 2015, https://doi.org/10.7314/APJCP.2015.16.9.3867
  5. The tumor marker CA 72-4 pp.2198-0713, 2017, https://doi.org/10.1007/s40664-017-0212-2
  6. Effects of different methods of anesthesia and analgesia on immune function and serum tumor marker levels in critically ill patients vol.14, pp.3, 2017, https://doi.org/10.3892/etm.2017.4762
  7. Cytokeratin-18 fragments predict treatment response and overall survival in gastric cancer in a randomized controlled trial vol.40, pp.3, 2018, https://doi.org/10.1177/1010428318764007