Significance of HE4 estimation in comparison with CA125 in diagnosis of ovarian cancer and assessment of treatment response
详细信息    查看全文
  • 作者:Elham O Hamed (1)
    Hydi Ahmed (1)
    Osama B Sedeek (4)
    Abeer M Mohammed (1)
    Ali A Abd-Alla (2)
    Hazem M Abdel Ghaffar (3)
  • 关键词:Human epididymis protein 4 ; HE4 ; Carbohydrate antigen125 ; CA125 ; Epithelial ; Ovarian cancer ; EOC
  • 刊名:Diagnostic Pathology
  • 出版年:2013
  • 出版时间:December 2013
  • 年:2013
  • 卷:8
  • 期:1
  • 全文大小:201KB
  • 参考文献:1. Rauh-Hain JA, Krivak TC, del Carmen MG, Olawaiye AB: ass="a-plus-plus">Ovarian cancer screening and early detection in the general population. / Rev Obstet Gynecol 2011,ass="a-plus-plus">4(1)ass="a-plus-plus">:15-1.
    2. Lee KR, Tavassoli FA, Prat J, Dietel M, Gersell DJ, Karseladze AI, Hauptmann S, Rutgers J: ass="a-plus-plus">WHO histological classification of tumours of the ovary (chapter 2). In / pathology and genetics of tumours of the breast and female genital organs. Edited by: Tavassoli FA, Devilee P. Lyon: IARC Pres; 2003:113-61.
    3. Nolen B, Marrangoni A, Velikokhatnaya L, Prosser D, Winans M, Gorelik E, Anna LA: ass="a-plus-plus">A serum based analysis of ovarian epithelial tumorigenesis. / Gynecol Oncol 2009,ass="a-plus-plus">112(1)ass="a-plus-plus">:47-4. <a class="external" href="http://dx.doi.org/10.1016/j.ygyno.2008.09.043">CrossRefa>
    4. Kurman RJ, Shih I-M: ass="a-plus-plus">Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer-shifting the paradigm. / Hum Pathol 2011,ass="a-plus-plus">42(7)ass="a-plus-plus">:918-31. <a class="external" href="http://dx.doi.org/10.1016/j.humpath.2011.03.003">CrossRefa>
    5. Hatice O, GoncaImir Y, Sema A, Meral C, Ersin T, Ali C: ass="a-plus-plus">Immunohistochemistry with apoptotic-antiapoptotic proteins (p53, p21, bax, bcl-2), c-kit, telomerase, and metallothionein as a diagnostic aid in benign, borderline, and malignant serous and mucinous ovarian tumors. / Diagn Pathol 2012, ass="a-plus-plus">7:124. <a class="external" href="http://dx.doi.org/10.1186/1746-1596-7-124">CrossRefa>
    6. Fauvet R, Dufornet C, Poncelet C, Uzan C, Hugol D, Darai E: ass="a-plus-plus">Expression of Pro apoptotic (p53, p21, bax, bak and fas) and anti-apoptotic (bcl-2 and bcl-x) proteins in serous versus mucinous borderline ovarian tumours. / J SurgOncol 2005, ass="a-plus-plus">92:337-43.
    7. Nielsen JS, Jakobsen E, Holund B, Bertelsen K, Jakobsen A: ass="a-plus-plus">Prognostic significance of p53, Her-2, and EGFR overexpression in borderline and epithelial ovarian cancer. / Int J Gynecol Cancer 2004, ass="a-plus-plus">14:1086-096. <a class="external" href="http://dx.doi.org/10.1111/j.1048-891X.2004.14606.x">CrossRefa>
    8. Havrilevsky L, Darcy K, Hamdan R, Priore RL, Leon J, Bell J, Berchuck A: ass="a-plus-plus">Prognostic significance of p53 mutation and p53 overerpression in advanced epithelial ovarian cancer: a gynecologic oncology group study. / J Clin Oncol 2003, ass="a-plus-plus">21:3814-825. <a class="external" href="http://dx.doi.org/10.1200/JCO.2003.11.052">CrossRefa>
    9. Viren A, Raheela K, Averil W, Robert S, Schalkwyk GV, Anish B, Sowter HM: ass="a-plus-plus">The Eag potassium channel as a new prognostic marker in ovarian cancer. / Diagn Pathol 2010, ass="a-plus-plus">5:78. <a class="external" href="http://dx.doi.org/10.1186/1746-1596-5-78">CrossRefa>
    10. Valentin L: ass="a-plus-plus">Use of morphology to characterize and manage common adnexal masses. / Best Pract Res Clin Obstet Gynaecol 2004, ass="a-plus-plus">18:71-9. <a class="external" href="http://dx.doi.org/10.1016/j.bpobgyn.2003.10.002">CrossRefa>
    11. Rosen DG, Wang L, Atkinson JN: ass="a-plus-plus">Potential markers that complement expression of CA125 in epithelial ovarian cancer. / Gynecol Oncol 2005, ass="a-plus-plus">99:267-77. <a class="external" href="http://dx.doi.org/10.1016/j.ygyno.2005.06.040">CrossRefa>
    12. Maggino T, Gadducci A, D’Addario V: ass="a-plus-plus">Prospective multicenter study on CA125 in postmenopausal pelvic masses. / Gynecol Oncol 1994, ass="a-plus-plus">54:117-23. <a class="external" href="http://dx.doi.org/10.1006/gyno.1994.1179">CrossRefa>
    13. Kobayashi H, Yamada Y, Sado T: ass="a-plus-plus">A randomized study of screening for ovarian cancer: a multicenter study in Japan. / Int J Gynecol Cancer 2008, ass="a-plus-plus">18:414-20. <a class="external" href="http://dx.doi.org/10.1111/j.1525-1438.2007.01035.x">CrossRefa>
    14. Yousef GM, Polymeris ME, Yacoub GM: ass="a-plus-plus">Parallel overexpression of seven kallikrein genes in ovarian cancer. / Cancer Res 2003, ass="a-plus-plus">63:2223-227.
    15. Galgano MT, Hampton GM, Frierson HF Jr: ass="a-plus-plus">Comprehensive analysis of HE4 expression in normal and malignant human tissues. / Mod Pathol 2006, ass="a-plus-plus">19:847-53.
    16. Drapkin R, von Horsten HH, Lin Y: ass="a-plus-plus">Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. / Cancer Res 2005, ass="a-plus-plus">65:2162-169. <a class="external" href="http://dx.doi.org/10.1158/0008-5472.CAN-04-3924">CrossRefa>
    17. Ruggeri G, Bandiera E, Zanotti L, Belloli S, Ravaggi A, Romani C: ass="a-plus-plus">HE4 and epithelial ovarian cancer: comparison and clinical evaluation of two immunoassays and a combination algorithm. / Clin Chim Acta 2011, ass="a-plus-plus">412:1447-453. <a class="external" href="http://dx.doi.org/10.1016/j.cca.2011.04.028">CrossRefa>
    18. Rien BJD, Gupta S, Dada R, Safi J, Michener C, Agarwal A: ass="a-plus-plus">Potential markers for detection and monitoring of ovarian cancer. / J Oncology 2011, ass="a-plus-plus">2011:475983.
    19. Aebi S, Castiglione M: ass="a-plus-plus">Newly and relapsed epithelial ovarian carcinoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. / Ann Oncol 2009,ass="a-plus-plus">20(Suppl 4)ass="a-plus-plus">:21-3.
    20. Sturgeon CM, Duffy MJ, Stenman U-H: ass="a-plus-plus">National academy of clinical biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. / Clin Chem 2008, ass="a-plus-plus">54:e11-e79. <a class="external" href="http://dx.doi.org/10.1373/clinchem.2008.105601">CrossRefa>
    21. Bast RC Jr: ass="a-plus-plus">Status of tumor markers in ovarian cancer screening. / J Clin Oncol 2003, ass="a-plus-plus">21:200-05. <a class="external" href="http://dx.doi.org/10.1200/JCO.2003.01.068">CrossRefa>
    22. Moore RG, Jaube-Raughley M, Brown AK: ass="a-plus-plus">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. / Am J Obstet Gynecol 2010, ass="a-plus-plus">203:e1-e6. <a class="external" href="http://dx.doi.org/10.1016/j.ajog.2010.03.043">CrossRefa>
    23. Kim YM, Whang DH, Park J, Kim SH, Lee SW, Park HA, Ha M, Choi KH: ass="a-plus-plus">Evaluation of the accuracy of serum human epididymis protein 4 in combination with CA125 for detecting ovarian cancer: a prospective case–control study in a Korean population. / Clin Chem Lab Med 2011,ass="a-plus-plus">49(3)ass="a-plus-plus">:527-34. <a class="external" href="http://dx.doi.org/10.1515/cclm.2011.085">CrossRefa>
    24. Huhtinen K, Suvitie P, Hiissa J, Junnila J, Huvila J, Kujari H: ass="a-plus-plus">Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. / Br J Cancer 2009, ass="a-plus-plus">100:1315-319. <a class="external" href="http://dx.doi.org/10.1038/sj.bjc.6605011">CrossRefa>
    25. Bordin L, Fiore C, Donà G, Andrisani A, Ambrosini G, Faggian D: ass="a-plus-plus">Evaluation of erythrocyte band 3 phosphotyrosine level, glutathione content, CA-125, and human epididymal secretory protein E4 as combined parameters in endometriosis. / Fertil Steril 2010, ass="a-plus-plus">94:1616-621. <a class="external" href="http://dx.doi.org/10.1016/j.fertnstert.2009.10.038">CrossRefa>
    26. Li J, Dowdy S, Tipton T: ass="a-plus-plus">HE4 as a biomarker for ovarian and endometrial cancer management. / Expert Rev Mol Diagn 2009, ass="a-plus-plus">9:555-66. <a class="external" href="http://dx.doi.org/10.1586/erm.09.39">CrossRefa>
    27. Montagnana M, Lippi G, Ruzzenente O: ass="a-plus-plus">The utility of serum human epididymis protein 4 (HE4) in patients with a pelvic mass. / Clin Lab Anal 2009, ass="a-plus-plus">23:331-35. <a class="external" href="http://dx.doi.org/10.1002/jcla.20340">CrossRefa>
    28. Gorp T, Cadron I, Despierre E, Daemen A, Leunen K, Amant F: ass="a-plus-plus">HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the risk of ovarian malignancy algorithm. / Br J Cancer 2011,ass="a-plus-plus">104(5)ass="a-plus-plus">:863-70. <a class="external" href="http://dx.doi.org/10.1038/sj.bjc.6606092">CrossRefa>
    29. Montagnana M, Danese E, Ruzzenente O, Bresciani V, Nuzzo T, Gelati M: ass="a-plus-plus">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 2011,ass="a-plus-plus">49(3)ass="a-plus-plus">:521-25. <a class="external" href="http://dx.doi.org/10.1515/cclm.2011.075">CrossRefa>
    30. Rafael M, Escudero JM, Augé JM, Xavier F, Laura F, Aureli T, Jose L, Jaume P: ass="a-plus-plus">HE4 a novel tumour marker for ovarian cancer: comparison with CA125 and ROMA algorithm in patients with gynecological diseases. / Tumour Biol 2011,ass="a-plus-plus">32(6)ass="a-plus-plus">:1087-095. <a class="external" href="http://dx.doi.org/10.1007/s13277-011-0204-3">CrossRefa>
    31. Park Y, Lee JH, Hong DJ, Lee EY, Kim HS: ass="a-plus-plus">Diagnostic performances of HE4 and CA125 for the detection of ovarian cancer from patients with various gynecologic and non-gynecologic diseases. / Clin Biochem 2011, ass="a-plus-plus">44:884-88. <a class="external" href="http://dx.doi.org/10.1016/j.clinbiochem.2011.04.011">CrossRefa>
    32. Bingle L, Cross SS, High AS: ass="a-plus-plus">WFDC2 (HE4): a potential role in the innate immunity of the oral cavity and respiratory tract and the development of adenocarcinomas of the lung. / Respir Res 2006, ass="a-plus-plus">7:61. <a class="external" href="http://dx.doi.org/10.1186/1465-9921-7-61">CrossRefa>
    33. Xi Z, LinLin M, Ye T: ass="a-plus-plus">Human epididymis protein 4 is a biomarker for transitional cell carcinoma in the urinary system. / J Clin Lab Anal 2009, ass="a-plus-plus">23:357-61. <a class="external" href="http://dx.doi.org/10.1002/jcla.20329">CrossRefa>
    34. Moore RG, Brown AK, Miller MC: ass="a-plus-plus">The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. / Gynecol Oncol 2008, ass="a-plus-plus">108:402-08. <a class="external" href="http://dx.doi.org/10.1016/j.ygyno.2007.10.017">CrossRefa>
    35. Moore RG, McMeekin DS, Brown AK: ass="a-plus-plus">A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. / Gynecol Oncol 2009, ass="a-plus-plus">112:40-6. <a class="external" href="http://dx.doi.org/10.1016/j.ygyno.2008.08.031">CrossRefa>
    36. Havrilesky LJ, Whitehead CM, Rubatt JM: ass="a-plus-plus">Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence. / Gynecol Oncol 2008, ass="a-plus-plus">110:374-82. <a class="external" href="http://dx.doi.org/10.1016/j.ygyno.2008.04.041">CrossRefa>
    37. Nolen B, Velikokhkatnaya L, Marrangoni A: ass="a-plus-plus">Serum biomarker panels for the discrimination of benign from malignant cases in patients with an adnexal mass. / Gynecol Oncol 2010, ass="a-plus-plus">117:440-45. <a class="external" href="http://dx.doi.org/10.1016/j.ygyno.2010.02.005">CrossRefa>
    38. Yurkovetsky Z, Skates S, Lomakin A: ass="a-plus-plus">Development of a multimarker assay for early detection of ovarian cancer. / J Clin Oncol 2010, ass="a-plus-plus">28:2159-166. <a class="external" href="http://dx.doi.org/10.1200/JCO.2008.19.2484">CrossRefa>
    39. Kobel M, Kalloger SE, Boyd N: ass="a-plus-plus">Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. / PLoS Med 2008, ass="a-plus-plus">5:e232. <a class="external" href="http://dx.doi.org/10.1371/journal.pmed.0050232">CrossRefa>
    40. Rustin GJ, Vergote I, Eisenhauer E, Pujade-Lauraine E, Quinn M: ass="a-plus-plus">Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA125 agreed by the Gynecological Cancer Intergroup (GCIG). / Int J Gynecol Cancer 2011, ass="a-plus-plus">21:419-23. <a class="external" href="http://dx.doi.org/10.1097/IGC.0b013e3182070f17">CrossRefa>
    41. Park Y, Kim Y, Lee EY, Lee JH, Kim HS: ass="a-plus-plus">Reference ranges for HE4 and CA125 in a large Asian population by automated assays and diagnostic performances for ovarian cancer. / Int J Cancer 2012,ass="a-plus-plus">130(5)ass="a-plus-plus">:1136-144. <a class="external" href="http://dx.doi.org/10.1002/ijc.26129">CrossRefa>
    42. Jacob F, Meier M, Caduff R, Goldstein D, Pochechueva T: ass="a-plus-plus">No benefit from combining HE4 and CA125 as ovarian tumor markers in a clinical setting. / Gynecol Oncol 2011, ass="a-plus-plus">121:487-91. <a class="external" href="http://dx.doi.org/10.1016/j.ygyno.2011.02.022">CrossRefa>
    43. Chang X, Ye X, Dong L, Cheng H, Cheng Y: ass="a-plus-plus">Human epididymis protein 4 (HE4) as a serum tumor biomarker in patients with ovarian carcinoma. / Int J Gynecol Cancer 2011,ass="a-plus-plus">21(5)ass="a-plus-plus">:852-58. <a class="external" href="http://dx.doi.org/10.1097/IGC.0b013e31821a3726">CrossRefa>
    44. Paek J, Lee SH, Yim GW, Lee M, Kim YJ: ass="a-plus-plus">Prognostic significance of human epididymis protein 4 in epithelial ovarian cancer. / Eur J Obstet Gynecol Reprod Biol 2011,ass="a-plus-plus">158(2)ass="a-plus-plus">:338-42. <a class="external" href="http://dx.doi.org/10.1016/j.ejogrb.2011.05.021">CrossRefa>
    45. Allard J, Somers E, Theil R, Moore RG: ass="a-plus-plus">Use of a novel biomarker HE4 for monitoring patients with epithelial ovarian cancer. / J Clin Oncol 2008, ass="a-plus-plus">26:5535.
  • 作者单位:Elham O Hamed (1)
    Hydi Ahmed (1)
    Osama B Sedeek (4)
    Abeer M Mohammed (1)
    Ali A Abd-Alla (2)
    Hazem M Abdel Ghaffar (3)

    1. Clinical Pathology Department, Faculty of Medicine, Sohag University, Sohag, 82524, Egypt
    4. Clinical Pathology Department, Faculty of Medicine, Assiut University, Assiut, Egypt
    2. Clinical Oncology Department, Faculty of Medicine, Sohag University, Sohag, 82524, Egypt
    3. Obstetrics & Gynecology Department, Faculty of Medicine, Sohag University, Sohag, Egypt
文摘
Background Human epididymis protein 4 (HE4) is a novel and specific biomarker for ovarian cancer. The aim of this study is to evaluate a new tumor marker, HE4, in comparison with CA125 in diagnosis of epithelial ovarian cancer (EOC) and benign gynecological diseases. Methods CA125 and HE4 serum levels were determined in 30 patients with epithelial ovarian cancer (21 serous, 6 endometrioid and 3 mucinous tumors), 20 patients with benign gynecological diseases (8 patients with ovarian cyst, 5 patients with endometriosis, 4 patients with fibroid and 3 patients with pelvic inflammatory disease) and 20 healthy women. CA125 and HE4 cut-offs were 35 U/ml and 150 pmol/l, respectively. Results Serum HE4 and CA125 concentrations were significantly higher in the ovarian cancer patients compared with those seen in patients with benign disease or in the healthy controls (p--.001 and p-lt;-.001 respectively). In the receiver operating characteristic analysis (ROC), the area under the curve (AUC) values for HE4 was 0.96 (95% confidence interval, 0.9-1.0) and CA125 was 0.82 (95% confidence interval, 0.7-0.94). Compared to CA125, HE4 had higher sensitivity (90% vs. 83.3%), specificity (95% vs. 85%), PPV (93.1% vs. 80.7%) and NPV (92.7% vs. 87.2%), the combination of HE4-?CA125 the sensitivity and PPV reached 96.7% and 97% respectively. Conclusion Measuring serum HE4 concentrations along with CA125 concentrations may provide higher accuracy for detecting epithelial ovarian cancer. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1060413168685759

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700