Preoperative measurement of serum CA-125 levels: is it useful in the risk assessment of low volume lymph node disease in cervical cancer?

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BACKGROUND: Elevated serum cancer antigen 125 (CA-125) is observed in some cervical cancers (CCs). Is the correlation of CA-125 with the presence of nodal events useful in predicting early metastasis to the lymph nodes?

METHODS: The study included 45 patients with CC FIGO (2009) stages IA1-IIA1 and known preoperative CA-125 concentration, surgery treated (05.2011-05.2014). Investigated pretreatment: age (pre-, postmenopausal), histological type, grade, confounding factors - prior cone biopsy, ovarian cyst, endometriosis, liver or colon pathology, concomitant malignancy. LN metastases (LNM) were defined as macro (MAC, >2mm) and/or micrometastases (mic, 0.2 - 2 mm), and LVLND as mic or/and ITC (single CC cells clusters) in LNs. Ultrastaging of all LNs (sentinel and non-sentinel, 4 μm thick slices/150 μm intervals) was performed with hematoxylin and eosin staining and with immunohistochemistry (IHC - AE1/AE3 cytokeratin antibodies). Non-parametrical analysis and receiver operating curve analysis were used to determine correlation between CA-125 and LNM including LVLND.

RESULTS: The median age was 55 (23-71). 806 LNs were extracted. LNM was found in 12, LVLND in 6 patients. LNM but not LVLND was correlated with higher grade (G2-G3, p<0.05). LVLND was positively correlated with premenopausal age (p<0.05) but not with tumor histology or grade. Liver disease only was found to influence CA-125 levels (p=0.064). There were no differences within CA-125 concentration among LVLND, LNM, and node-negative patients groups, however a trend was found between higher CA-125 and lower LVLND risk.

CONCLUSIONS: Elevated levels of CA-125 may be less likely due to LVLND than to LN positivity. Grade is an important feature in prediction of LNM but not LVLND. CA-125 level was found to be not predictive of LNM nor LVLND, as confirmed by ultrastaging.

1. Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. Lancet Oncol. 2012 Aug;13(8):790-801. DOI: 10.1016/S1470-2045(12)70211-5

2. Reports based on the data the Oncology Centre:, Access: 10.12.2017 05.04.2017.

3. Høgdall EV, Christensen L, Kjaer SK, Blaakaer J, Kjaerbye-Thygesen A, Gayther S, et al. CA125 expression pattern, prognosis and correlation with serum CA125 in ovarian tumor patients. From The Danish “MALOVA” Ovarian Cancer Study. Gynecol Oncol. 2007 Mar;104(3):508-15. DOI: 10.1016/j.ygyno. 2006.09.028

4. Scharl A, Crombach G, Vierbuchen M, Müsch H, Bolte A. CA 125 in normal tissues and carcinomas of the uterine cervix, endometrium and fallopian tube. I. Immunohistochemical detection. Arch Gynecol Obstet. 1989 Jun;244(2):103-12. DOI: 10.1007/BF00931381

5. Sadowski EA, Robbins JB, Guite K, Patel-Lippmann K, Del Rio AM, Kushner DM, et al. Preoperative pelvic MRI and serum cancer antigen-125: selecting women with grade 1 endometrial cancer for lymphadenectomy. AJR Am J Roentgenol. 2015 Nov;205(5):W556-64. DOI: 10.2214/AJR.14.13746

6. Rizzuto I, Stavraka C, Chatteriee J, Borley J, Hopkins TG, Gabra H, et al. Risk of Ovarian Cancer Relapse Score: a prognostic algorithm to predict relapse following treatment for advanced ovarian cancer. Int J Gynecol Cancer. 2015 Mar;25(3):416-22. DOI: 10.1097/IGC.0000000000000361

7. Tsai CC, Liu YS, Huang EY, Huang SC, Chang HW, Tseng CW, ChangChien CC et al. Value of preoperative serum CA125 in early-stage adenocarcinoma of the uterine cervix without pelvic lymph node metastasis. Gynecol Oncol. 2006 Mar;100(3):591-5. DOI: 10.1016/j.ygyno.2005.09.049

8. Gadducci A, Tana R, Cosio S, Genazzani AR. The serum assay of tumour markers in the prognostic evaluation, treatment monitoring and follow-up of patients with cervical cancer: a review of the literature. Crit Rev Oncol Hematol. 2008 Apr;66(1):10-20. DOI: 10.1016/j. critrevonc.2007.09.002

9. Porika M, Vemunoori AK, Tippani R, Mohammad A, Bollam SR, Abbagani S. Squamous cell carcinoma antigen and cancer antigen 125 in southern Indian cervical cancer patients. Asian Pac J Cancer Prev. 2010 Jun;11(6):1745-7.

10. Takeda M, Sakuragi N, Okamoto K, Todo Y, Minobe S, Nomura E, et al. Preoperative serum SCC, CA125, and CA19-9 levels and lymph node status in squamous cell carcinoma of the uterine cervix. Acta Obstet Gynecol Scand. 2002 May;81(5):451-7. DOI: 10.1034/j.1600-0412.2002.810513.x

11. Koper NP, Thomas CM, Dorn KE, Schijf CP. Improvement of clinical staging in cervical cancer with serum squamous cell carcinoma antigen and CA 125 determinations. Gynecol Oncol. 1997 Mar;64(3):473-6. DOI: 10.1006/gyno.1996.4581

12. Avall-Lundqvist EH, Sjövall K, Nilsson BR, Eneroth PH. Prognostic significance of pretreatment serum levels of squamous cell carcinoma antigen and CA 125 in cervical carcinoma. Eur J Cancer. 1992;28A(10):1695-702. DOI: 10.1016/0959-8049(92)90071-9

13. Davelaar EM, van de Lande J, von Mensdorff-Pouilly S, Blankenstein MA, Verheijen RH, Kenemans P. A combination of serum tumor markers identifies high-risk patients with early-stage squamous cervical cancer. Tumour Biol. 2008;29(1):9-17. DOI: 10.1159/000132566

14. Ueda Y, Enomoto T, Kimura T, Miyatake T, Yoshiho K, Fujita M, et al. Serum biomarkers for early detection of gynecologic cancers. Cancers (Basel). 2010 Jun 14;2(2):1312-27. DOI: 10.3390/cancers2021312

15. Bats A, Mathevet P, Buenerd A, Orliaquet I, Mery E, Zerdoud S, et al. The sentinel node technique detects unexpected drainage pathways and allows nodal ultrastaging in early cervical cancer: insights from the multicenter prospective SENTICOL study. Ann Surg Oncol. 2013 Feb;20(2):413-22. DOI: 10.1245/s10434-012-2597-7

16. Borras G, Molina R, Xercevanis J, Ballesta A, Iglesias J. Tumor antigens CA 19.9, CA 125, and CEA in carcinoma of the uterine cervix. Gynecol Oncol. 1995 May;57(2):205-11. DOI: 10.1006/gyno.1995.1126

17. Kotowicz B, Kaminska J, Fuksiewicz M, Kowalska M, Jonska-Gmyrek J, Gawrychowski K, et al. Clinical significance of serum CA-125 and soluble tumor necrosis factor receptor type I in cervical adenocarcinoma patients. Int J Gynecol Cancer. 2010 May;20(4):588-92. DOI: 10.1111/IGC.0b013e3181d5c27a

18. Yamazaki H, Todo Y, Okamoto K, Yamashiro K, Kato H. Pretreatment risk factors for parametrial involvement in FIGO stage IB1 cervical cancer. J Gynecol Oncol. 2015 Oct;26(4):255-61. DOI: 10.3802/jgo.2015.26.4.255

19. Darai E, Rouzier R, Ballester M, Barranger E, Coutant C. Sentinel lymph node biopsy in gynaecological cancers: the importance of micrometastases in cervical cancer. Surg Oncol. 2008 Sep;17(3):227-35. DOI: 10.1016/j.suronc.2008.04.002

20. Slama J, Dundr P, Dusek L, Fischerova D, Pinakavova I, Vrzackova P, et al. Sentinel lymph node status in patients with locally advanced cervical cancers and impact on neoadjuvant chemotherapy. Gynecol Oncol. 2012 May;125(2):303-6. DOI: 10.1016/j.ygyno.2012.02.010

21. Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet. 2009 May;105(2):103-4. DOI: 10.1016/j. ijgo.2009.02.009 DOI: 10.1016/j.ijgo.2009.02.012

22. Schwartz GF, Giuliano AE, Veronesi U. Proceedings of the consensus conference on the role of sentinel lymph node biopsy in carcinoma of the breast. April 15-22, 2001. Philadelphia. Pennsylvania. Cancer. 2002 May 15;94(10):2542-51. DOI: 10.1002/cncr.10539

23. Singletary SE, Greene FL. Revision of breast cancer staging: the 6th edition of the TNM Classification. Semin Surg Oncol. 2003 Nov;21(1):53-9. DOI: 10.1002/ssu.10021

24. Goldberg GL, Sklar A, O’Hanlan KA, Levine PA, Runowicz CD. CA-125: a potential prognostic indicator in patients with cervical cancer? Gynecol Oncol. 1991 Mar;40(3):222-4. DOI: 10.1016/0090-8258(90)90281- O

25. Divine LM, Kizer NT, Hagemann AR, Pittman ME, Chen L, Powell MA, et al. Clinicopathologic characteristics and survival of patients with gynecologic malignancies metastatic to the brain. Gynecol Oncol. 2016 Jul;142(1):76-82. DOI: 10.1016/j.ygyno.2016.04.030

26. Dasari S, Wudayagiri R, Valluru L. Cervical cancer: biomarkers for diagnosis and treatment. Clin Chim Acta. 2015 May 20;445:7-11. DOI: 10.1016/j. cca.2015.03.005

27. Rimel BJ, Burke WM, Higgins RV, Lee PS, Lutman CV, Parker L. Improving quality and decreasing cost in gynecologic oncology care. Society of gynecologic oncology recommendations for clinical practice. Gynecol Oncol. 2015 May;137(2):280-4. DOI: 10.1016/j.ygyno. 2015.02.021

28. Hoogendam JP, Zaal A, Rutten EG, Heijnen CJ, Kenter GG, Veldhuis WB, et al. Detection of cervical cancer recurrence during follow-up: a multivariable comparison of 9 frequently investigated serum biomarkers. Gynecol Oncol. 2013 Dec;131(3):655-60. DOI: 10.1016/j.ygyno.2013.10.016

29. Kupets R, Giede KC, Power P, Agrawal A; Executive of the Society Gynecologic Oncology of Canada. The investigations required before referring a patient to a gynecologic oncologist. J Obstet Gynaecol Can. 2016 Feb;38(2):164-7. DOI: 10.1016/j.jogc.2015.12.016

30. Togami S, Sasajima Y, Kasamatsu T, Oda-Otomo R, Okada S, Ishikawa M, et al. Immunophenotype and human papillomavirus status of serous adenocarcinoma of the uterine cervix. Pathol Oncol Res. 2015 Apr;21(2):487-94. DOI: 10.1007/s12253-014-9854-y

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