The Role of cancer antigen 125 (Ca 125), Human Epididymis Protein 4 (HE4), Soluble Mezotelin Related Protein (SMRP), Folate Receptor Alpha (FOLRα) in Estimation of Malignancy Risk in Pelvic Masses

Abstract

An adnexal mass is a common gynecologic problem and malignancy must be excluded for any mass that is not clearly benign. Since ovarian cancer is the most common cause of gynecologic cancer death. The differential diagnosis of benign and malignant neoplastic masses is important for referring the patient to the gynecologic oncologist. Use of serum biomarkers for the diagnosis of ovarian cancer is an active area of investigation. Our research was performed between September 2014 and January 2017. Between 18 and 90 ages, 95 operated patients because of pelvic masses are included. Preoperatively CA 125, HE4, SMRP, FOLRα levels are measured for each patient and relationship between tumor marker levels and pathological reports is examined. HE4 and SMRP levels are found higher in malignant masses significantly. But CA 125 and FOLRα levels are not related with malignancy. HE4 and SMRP can be used as a serum biomarker for prediction of ovarian cancer according to our study. However the data should be supported with more studies.

Keywords

• Pelvic Mass
• Ca 125 Antigen
• HE4 protein
• SMRP protein
• Folate Receptor alpha

Pelvik Kitlelerin Malignite Riski Değerlendirilmesinde Kanser Antijeni 125 (Ca 125), Human Epididymis Protein 4 (HE4), Soluble mesothelin-related protein (SMRP) ve Folat Reseptör Alfa (FOLRα) Ölçümünün Yeri

Abstract

Adneksiyal kitle yaygın jinekolojik sorundur ve kitleler için malignite net bir şekilde dışlanmalıdır. Over kanserleri en mortal jinekolojik kanserlerdir. Benign ve malign adneksiyal kitlelerin ayırıcı tanısı, hastanın jinekolojik onkologa yönlendirilmesinde önemlidir. Over kanseri tanısında serum biyomarkerlarının kullanılması yaygın olarak araştırılmaktadır. Çalışmamız Ekim 2014 – Ocak 2017 tarihleri arasında yapıldı. Pelvik kitlesi olan 18 ve 90 yaşları arasında 95 hasta seçildi. Her hasta için preooperatif CA 125, HE4, SMRP, FOLRα seviyeleri ölçüldü ve patoloji sonuçları ile kan sonuçları arasındaki ilişki incelendi. HE4 ve SMRP malign kitlelerde önemli ölçüde yüksek bulundu. Fakat Ca 125 ve FOLRα seviyeleri malingnitede anlamsız saptandı. Çalışmamıza göre; HE4 ve SMRP over kanserini ön görmede kullanılabilir. Fakat daha fazla çalışmalar ile desteklenmelidir.

Keywords

• Pelvik Kitle
• Kanser Antijeni 125
• HE4
• SMRP
• Folat Reseptör Alfa

References

1. Heintz, A., et al., Carcinoma of the ovary. International Journal of Gynecology & Obstetrics, 2006. 95: p. S161-S192.
2. Ferlay, Jacques, et al. "Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012." International journal of cancer 136.5 (2015): E359-E386.
3. Andersen, M.R., et al., Combining a symptoms index with CA 125 to improve detection of ovarian cancer. Cancer, 2008. 113(3): p. 484-489.
4. Wolk, A., et al., Long-term fatty fish consumption and renal cell carcinoma incidence in women. Jama, 2006. 296(11): p. 1371-1376.
5. Wentzensen, Nicolas, et al. "Ovarian cancer risk factors by histologic subtype: an analysis from the ovarian cancer cohort consortium." Journal of Clinical Oncology 34.24 (2016): 2888.)
6. Arvas M, Gezer A “Ailevi Over Kanseri, BRCA Genleri ve Over Kanseri Tarama Programlar” Türk Jinekolojik Onkoloji Dergisi 2004. 7(2) p.
7. Goldstein, S.R., Postmenopausal adnexal cysts: how clinical management has evolved. American journal of obstetrics and gynecology, 1996. 175(6): p. 1498-1501.
8. Carlson, K.J., S.J. Skates, and D.E. Singer, Screening for ovarian cancer. Annals of internal medicine, 1994. 121(2): p. 124-132.

9. Taylor, K. and P.E. Schwartz, Screening for early ovarian cancer. Radiology, 1994. 192(1): p. 1-10.
10. Sankaranarayanan, R. and J. Ferlay, Worldwide burden of gynaecological cancer: the size of the problem. Best practice & research Clinical obstetrics & gynaecology, 2006. 20(2): p. 207-225.
11. Moore, R.G., et al., A novel multiple marker bioassay utilizing HE4 and CA-125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecologic oncology, 2009. 112(1): p. 40-46.
12. Moore, R.G., et al., Comparison of a novel multiple marker assay vs the Risk of Malignancy Index for the prediction of epithelial ovarian cancer in patients with a pelvic mass. American journal of obstetrics and gynecology, 2010. 203(3): p. 228. e1-228. e6.
13. Van Gorp, T., et al., HE4 and CA-125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm. British journal of cancer, 2011. 104(5): p. 863-870.
14. Montagnana, M., et al., 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? Clinical Chemistry and Laboratory Medicine, 2011. 49(3): p. 521-525.
15. Kim, Y.M., et al., 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. Clinical chemistry and laboratory medicine, 2011. 49(3): p. 527-534.
16. Paek, J., et al., Prognostic significance of human epididymis protein 4 in epithelial ovarian cancer. European Journal of Obstetrics & Gynecology and Reproductive Biology, 2011. 158(2): p. 338-342.
17. Rottem, S., et al., Classification of ovarian lesions by high‐frequency transvaginal sonography. Journal of clinical ultrasound, 1990. 18(4): p. 359-363.
18. Piver, M.S., et al. Epidemiology and etiology of ovarian cancer. in Seminars in oncology. 1991.
19. Fortner, Renée T., et al. "Ovarian cancer early detection by circulating CA 125 in the context of anti‐CA 125 autoantibody levels: Results from the EPIC cohort." International journal of cancer 142.7 (2018): 1355-1360.)
20. Ionescu, Crîngu Antoniu, et al. "Correlation of ultrasound features and the Risk of Ovarian Malignancy Algorithm score for different histopathological subtypes of benign adnexal masses." Medicine 97.31 (2018): e11762.
21. Parashkevova, Asya, et al. "Preoperative CA-125 Value as a Predictive Factor for Postoperative Outcome in First Relapse of Platinum-sensitive Serous Ovarian Cancer." Anticancer research 38.8 (2018): 4865-4870.
22. 22. Zhang, Lei, Ying Chen, and Ke Wang. "Comparison of CA125, HE4, and ROMA index for ovarian cancer diagnosis." Current Problems in Cancer (2018)
23. O'connell, G.J., et al., Predictive value of CA 125 for ovarian carcinoma in patients presenting with pelvic masses. Obstetrics & Gynecology, 1987. 70(6): p. 930-931.
24. Patsner, B. and W.J. Mann, The value of preoperative serum CA 125 levels in patients with a pelvic mass. American journal of obstetrics and gynecology, 1988. 159(4): p. 873-876.
25. O’Shannessy et al. Serum folate receptor alpha, mesothelin and megakaryocyte potentiating factor in ovarian cancer: association to disease stage and grade and comparison to CA125 and HE4 Journal of Ovarian Research 2013, 6:29 )
26. Lowe, K.A., et al., Effects of personal characteristics on serum CA-125, mesothelin, and HE4 levels in healthy postmenopausal women at high-risk for ovarian cancer. Cancer Epidemiology and Prevention Biomarkers, 2008. 17(9): p. 2480-2487.
27. Bast, R.C., Status of tumor markers in ovarian cancer screening. Journal of Clinical Oncology, 2003. 21(10 suppl): p. 200s-205s.
28. Shah, C.A., et al., Influence of ovarian cancer risk status on the diagnostic performance of the serum biomarkers mesothelin, HE4, and CA-125. Cancer Epidemiology and Prevention Biomarkers, 2009. 18(5): p. 1365-1372.
29. Chang, K. and I. Pastan, Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers. Proceedings of the National Academy of Sciences, 1996. 93(1): p. 136-140.
30. Scholler, N., et al., Development of a CA-125-mesothelin cell adhesion assay as a screening tool for biologics discovery. Cancer letters, 2007. 247(1): p. 130-136.
31. Chang, K., et al., Characterization of the antigen (CAK1) recognized by monoclonal antibody K1 present on ovarian cancers and normal mesothelium. Cancer research, 1992. 52(1): p. 181-186.
32. Blaustein, A., Peritoneal mesothelium and ovarian surface cells--shared characteristics. International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists, 1983. 3(4): p. 361-375.
33. Okamura, H., et al., Structural changes and cell properties of human ovarian surface epithelium in ovarian pathophysiology. Microscopy research and technique, 2006. 69(6): p. 469-481.
34. Dubeau, L., The cell of origin of ovarian epithelial tumours. The lancet oncology, 2008. 9(12): p. 1191-1197.
35. Okamura, H. and H. Katabuchi, Detailed morphology of human ovarian surface epithelium focusing on its metaplastic and neoplastic capability. Italian journal of anatomy and embryology= Archivio italiano di anatomia ed embriologia, 2000. 106(2 Suppl 2): p. 263-276.
36. Kurman, R.J. and I.-M. Shih, Pathogenesis of ovarian cancer. Lessons from morphology and molecular biology and their clinical implications. International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists, 2008. 27(2): p. 151.
37. McIntosh, M., et al., Combining CA 125 and SMR serum markers for diagnosis and early detection of ovarian carcinoma. Gynecologic oncology, 2004. 95(1): p. 9-15.
38. Shah CA et.al “Influence of ovarian cancer risk status on the diagnostic performance of the serum biomarkers mesothelin, HE4, and CA125” ) Cancer Epidemiol Biomarkers Prev. 2009 May;18(5):1365-72
39. Fritz-Rdzanek, A., et al., HE4 protein and SMRP: Potential novel biomarkers in ovarian cancer detection. Oncology letters, 2012. 4(3): p. 385-389.
40. Hellström, I., et al., The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer research, 2003. 63(13): p. 3695-3700.
41. Moore, R.G., et al., The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecologic oncology, 2008. 108(2): p. 402-408.
42. Andersen, M.R., et al., Use of a Symptom Index, CA-125, and HE4 to predict ovarian cancer. Gynecologic oncology, 2010. 116(3): p. 378-383.
43. Hekman, Marlène CH, et al. "Improved intraoperative detection of ovarian cancer by folate receptor alpha targeted dual-modality imaging." Molecular pharmaceutics 14.10 (2017): 3457-3463.
44. Basal, E., et al., Functional folate receptor alpha is elevated in the blood of ovarian
45. Kalli, K.R., et al., Folate receptor alpha as a tumor target in epithelial ovarian cancer. Gynecologic oncology, 2008. 108(3): p. 619-626.