Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Pattern of Tissue Expression of CA-125 and HE4 in Primary Epithelial Ovarian Tumours and Correlation with Serum CA-125 Levels

  • Published : 2013.08.30
Download PDF
⟨ Previous Next ⟩

Abstract

The objective of this study is to assess tissue expression of CA-125 and HE4 protein in primary benign and malignant epithelial tumours of the ovary and correlate with serum CA-125 levels. A total of 100 formalin-fixed, paraffin embedded sections of ovarian tumours which included serous adenoma (11), mucinous adenoma (42), serous carcinoma (20), mucinous carcinoma (12) and endometrioid carcinoma (15), histologically diagnosed between $1^{st}$ January 2004 to $31^{st}$ December 2012 at the University Malaya Medical Centre, were stained for HE4 (rabbit polyclonal antibody, Abcam, UK) and CA-125 (mouse monoclonal antibody clone: OC125, Cell Marque Corporation, Rocklin, California, USA). Pre-operative serum CA-125 levels were obtained from the laboratory information system. Immunoscore (I score) for HE4 and CA-125 was given based on the intensity of staining and percentage of positive tumour cells and considered significant when it was >50 (intensity of staining multiplied by percentage of positive tumour cells). Serum CA-125 levels were compared with the I score of HE4 and CA-125 in tissues. We noted that the CA-125 levels in serum and tissues were significantly raised in malignant compared to benign ovarian tumours (p value<0.05). Tissue expression of HE4 protein was also significantly raised in malignant tumours compared to benign tumours (p value<0.05). We conclude that HE4 can be a useful tissue immunomarker in addition to CA-125.

Keywords

References

  1. Anastasi E, Marchei GG, Viggiani V, et al (2010). HE4: a new potential early biomarker for the recurrence of ovarian cancer. Tum Biol, 31, 113-9. https://doi.org/10.1007/s13277-009-0015-y
  2. Bast RC Jr, Feeny M, Lazarus H, et al (1981). Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest, 68, 1331-7. https://doi.org/10.1172/JCI110380
  3. Bast RC, Badgwell D, Lu Z, et al (2005). New tumor markers: CA125 and beyond. Int J Gynecol Cancer, 15, 274-81. https://doi.org/10.1111/j.1525-1438.2005.00441.x
  4. Bergmann JF, Beaugrand M, Labadie H, et al (1986). CA 125 (ovarian tumour-associated antigen) in ascitic liver diseases. Clin Chim Acta, 155, 163-5. https://doi.org/10.1016/0009-8981(86)90278-0
  5. Breitenecker G, Neunteufel W, Bieglmayer C, et al (1989). Comparison between tissue and serum content of CA 125, CA 19-9 and carcinoembryonic antigen in ovarian tumours. Int J Gynecol Pathol, 8, 97-102. https://doi.org/10.1097/00004347-198906000-00002
  6. Chang X, Ye X, Cheng H, et al (2011). Human epididymis protein 4 (HE4) as a serum tumor biomarker in patients with ovarian carcinoma. Int J Gynec Cancer, 5, 852-8.
  7. Drapkin R, von Horsten HH, Lin Y, et al (2005). Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res, 65, 2162-9. https://doi.org/10.1158/0008-5472.CAN-04-3924
  8. Escudero JM, Auge JM, Filella X, et al (2011). Comparison of serum human epididymis protein 4 with cancer antigen 125 as a tumor marker in patients with malignant and nonmalignant diseases. Clin Chem, 57, 1534-44. https://doi.org/10.1373/clinchem.2010.157073
  9. Freydanck MK, Laubender RP, Rack B, et al (2012). Two-marker combinations for pre-operative discrimination of benign and malignant ovarian masses. Anticancer Res, 32, 2003-8.
  10. Galgano MT, Hampton GM, Frierson HF Jr, et al (2006). Comprehensive analysis of HE4 expression in normal and malignant human tissues. Mod Pathol, 19, 847-53.
  11. Goonewardene TI, Hall MR, Rustin GJ (2007). Management of symptomatic patients on follow-up for ovarian cancer with rising CA-125 concentrations. Lancet Oncol, 8, 813-21. https://doi.org/10.1016/S1470-2045(07)70273-5
  12. Hala AA, Hany AL, Samar MS, et al (2010). HE4 and mesothelin: Novel biomarkers of ovarian carcinoma in patients with pelvic masses. Asian Pac J Cancer Prev, 11, 111-6.
  13. Hellstrom I, Hellstrom KE (2008). SMRP and HE4 as Biomarkers for Ovarian Carcinoma When Used Alone and in Combination with CA125 and/or Each Other. Ovarian Cancer, 622, 15-21. https://doi.org/10.1007/978-0-387-68969-2_2
  14. Hellstrom I, Raycraft J, Hayden-Ledbetter M, et al (2003). The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res, 63, 3695-700.
  15. Hogdall EV, Christensen L, Kjaer SK, et al (2007). CA125 expression pattern, prognosis and correlation with serum CA125 in ovarian tumor patients. From The Danish “MALOVA” Ovarian Cancer Study. Gynecol Oncol, 104, 508-15. https://doi.org/10.1016/j.ygyno.2006.09.028
  16. Holcomb K, Vucetic Z, Miller MC, et al (2011). Human epididymis protein 4 offers superior specificity in the differentiation of benign and malignant adnexal masses in premenopausal women. Am J Obstet Gynecol, 205, 1-6. https://doi.org/10.1016/j.ajog.2011.05.029
  17. Huhtinen K, Suvitie P, Hiissa J, et al (2009). Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer, 100, 1315-9. https://doi.org/10.1038/sj.bjc.6605011
  18. Kim YM, Whang DH, Park J, et al (2011). Evaluation of the accuracy of serum human epididymis protein 4 in combination with CA 125 for detecting ovarian cancer: a prospective case-control study in a Korean population. Clin Chem Lab Med, 49, 527-34.
  19. Kirchoff C, Habben I, Ivell R, et al (1991). A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors. Biol Reprod, 45, 350-7. https://doi.org/10.1095/biolreprod45.2.350
  20. Kobel M, Kalloger SE, Carrick J, et al (2009). A limited panel of immunomarkers can reliably distinguish between clear cell and high-grade serous carcinoma of the ovary. Am J Surg Pathol, 33, 14-21. https://doi.org/10.1097/PAS.0b013e3181788546
  21. Kondalsamy-Chennakesavan S, Hacketal A, Bowtell D, et al (2013). Differentiating stage 1 epithelial ovarian cancer from benign ovarian tumours using a combination of tumour markers HE4, CA125, and CEA and patient’s age. Gynecol Oncol, 129, 467-71. https://doi.org/10.1016/j.ygyno.2013.03.001
  22. Lenhard M, Stieber P, Hertlein L, et al (2011). The diagnostic accuracy of two human epididymis protein 4 (HE4) testing systems in combination with CA125 in the differential diagnosis of ovarian masses. Clin Chem Lab Med, 49, 2081-8.
  23. Lim GCC, Rampal S, Halimah Y (2008). Cancer incidence in Peninsular Malaysia 2003-2005.The Third Report of the National Cancer Registry, National Cancer Registry, Ministry of Health Malaysia, Kuala Lumpur.
  24. Madore J, Ren F, Filali-Mouhim A, et al (2010). Characterisation of the molecular differences between ovarian endometrioid carcinoma and ovarian serous carcinoma. J Pathol, 220, 392-400.
  25. Markman M (1997). The role of CA-125 in the management of ovarian cancer. Oncologist, 2, 6-9.
  26. Molina R, Escudero JM, Auge JM, et al (2011). HE4 a novel tumour marker for ovarian cancer: comparison with CA 125 and ROMA algorithm in patients with gynaecological diseases. Tumour Biol, 32, 1087-95. https://doi.org/10.1007/s13277-011-0204-3
  27. Montagnana M, Danese E, Ruzzenente O, et al (2011). The ROMA (Risk of Ovarian Malignancy Algorithm) for estimating the risk of epithelial ovarian cancer in women presenting with pelvic mass: is it really useful? Clin Chem Lab Med, 49, 521-5.
  28. Moore RG, McMeekin DS, Brown AK, et al (2009). A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol, 112, 40-6. https://doi.org/10.1016/j.ygyno.2008.08.031
  29. Paramasivam M, Tripcony I, Crandon A, et al (2005). Prognostic importance of preoperative CA-125 in International Federation of Gynecology and Obstetrics stage I epithekial ovarian cancer: an Australian multicenter study. J Clin Oncol, 23, 5938-42. https://doi.org/10.1200/JCO.2005.08.151
  30. Park YJ, Lee JH, Hong DJ, et al (2011). Diagnostic performances of HE4 and CA125 for the detection of ovarian cancer from patients with various gynecologic and non-gynecologic diseases. Clin Biochem, 44, 884-8. https://doi.org/10.1016/j.clinbiochem.2011.04.011
  31. Rosen DG, Wang L, Atkinson JN, et al (2005). Potential markers that complement expression of CA125 in epithelial ovarian cancer. Gynecol Oncol, 99, 267-77. https://doi.org/10.1016/j.ygyno.2005.06.040
  32. Ruggeri G, Bandiera E, Zanotti L, et al (2011). HE4 and epithelial ovarian cancer: comparison and clinical evaluation of two immunoassays and algorithm. Clin Chim Acta, 412, 1447-53. https://doi.org/10.1016/j.cca.2011.04.028
  33. Shah CA, Lowe KA, Paley P (2009). Influence of ovarian cancer risk status on the diagnostic performance of the serum biomarkers mesothelin, HE4, and CA125. Cancer Epidemiol Biomarkers Prev, 18, 1365-72. https://doi.org/10.1158/1055-9965.EPI-08-1034
  34. Strugeon CM, Duffy MJ, Stenman UH, et al (2008). National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for the use of tumour markers in testicular, prostatic, colorectal, breast and ovarian cancer. Clin Chem, 54, 11-79. https://doi.org/10.1373/clinchem.2008.105601
  35. Terry K, Sluss P, Skates S, et al (2004). Blood and urine markers for ovarian cancer: a comprehensive review. Dis Markers, 20, 53-70. https://doi.org/10.1155/2004/241982
  36. Urban N, Thorpe J, Karlan BY, et al (2012). Interpretation of single and serial measures of HE4 and CA125 in asymptomatic women at high risk for ovarian cancer. Cancer Epidemiol Biomarkers Prev, 12, 2087-94.

Cited by

  1. HE4 as a Serum Biomarker for ROMA Prediction and Prognosis of Epithelial Ovarian Cancer vol.15, pp.1, 2014, https://doi.org/10.7314/APJCP.2014.15.1.101
  2. Is Target Oriented Surgery Sufficient with Borderline Ovarian Tumors? - Role of Accompanying Pathologies vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6749
  3. Level and Evaluation of Tumor Marker CA-125 in Ovarian Cancer Patients in Khyber Pakhtunkhwa, Pakistan vol.16, pp.1, 2015, https://doi.org/10.7314/APJCP.2015.16.1.185
  4. Prognostic value of serum and tissue HE4 expression in ovarian cancer: a systematic review with meta-analysis of 90 studies vol.18, pp.4, 2018, https://doi.org/10.1080/14737159.2018.1457436