妊娠期卵巢肿瘤标记物测定的临床价值
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摘要
妊娠期卵巢肿瘤的诊断有一定难度,卵巢肿瘤标记物检测是一种简便而又无创的检查手段,可辅助临床医生判断肿瘤的良恶性,但部分肿瘤标记物的水平可能受妊娠生理或病理的影响,不能轻易用非妊娠期的标准来判读,正确理解其检测价值可提高妊娠期卵巢肿瘤早期诊断水平,改善母儿预后。本文将对临床常用的10种卵巢肿瘤标记物在妊娠期的表达和意义作详细讨论。
Conducting a diagnosis of ovarian malignancy can be difficult in pregnant women. However, measuring tumor markers in maternal serum is simple and noninvasive. It can help to differentiate benign tumors from malignant ones. Partial markers can be affected by the physiological or pathological variation during pregnancy so that it can't be easily judged by non-gestational criteria. Correctly comprehending the significance of them can facilitate the early diagnosis of ovarian cancer in pregnant women and improve the prognosis of both mother and fetus. This article summarized the expression and significance of ten ovarian tumor markers commonly used in clinical practice in pregnant women.
Conducting a diagnosis of ovarian malignancy can be difficult in pregnant women. However, measuring tumor markers in maternal serum is simple and noninvasive. It can help to differentiate benign tumors from malignant ones. Partial markers can be affected by the physiological or pathological variation during pregnancy so that it can't be easily judged by non-gestational criteria. Correctly comprehending the significance of them can facilitate the early diagnosis of ovarian cancer in pregnant women and improve the prognosis of both mother and fetus. This article summarized the expression and significance of ten ovarian tumor markers commonly used in clinical practice in pregnant women.
引文
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[2] Mukhopadhyay A,Shinde A,Naik R.Ovarian cysts and cancer in pregnancy[J].Best Pract Res Clin Obstet Gynaecol,2016,33 ∶58-72.
[3] Aslam N,Ong C,Woelfer B,et al.Serum CA125 at 11-14 weeks of gestation in women with morphologically normal ovaries[J].BJOG,2000,107(5)∶689-690.
[4] Han SN,Lotgerink A,Gziri MM,et al.Physiologic variations of serum tumor markers in gynecological malignancies during pregnancy:a systematic review[J].BMC Med,2012,10(1)∶1-10.
[5] Sarandakou A,Protonotariou E,Rizos D.Tumor markers in biological fluids associated with pregnancy[J].Crit Rev Clin Lab Sci,2007,44(2)∶151-178.
[6] Bon GG,Kenemans P,Verstraeten AA,et al.Maternal serum Ca125 and Ca15-3 antigen levels in normal and pathological pregnancy.[J].Fetal Diagn Ther,2001,16(3)∶166-172.
[7] Amampai R,Suprasert P.Cancer antigen 125 during pregnancy in women without ovarian tumor is not often rising[J].Obstet Gynecol Int,2018 ∶8141583.
[8] Lu J,Zheng Z,Zhang Q,et al.Measurement of HE4 and CA125 and establishment of reference intervals for the ROMA index in the sera of pregnant women[J].J Clin Lab Anal,2018,32(5)∶e22368.
[9] Moore RG,Miller MC,Eklund EE,et al.Serum levels of the ovarian cancer biomarker HE4 are decreased in pregnancy and increase with age[J].Am J Obstet Gynecol,2012,206(4)∶349.e1-e7.
[10] Wang Z,Zhou F,Xiao X,et al.Serum levels of human epididymis protein 4 are more stable than cancer antigen 125 in early and mid-term pregnancy[J].J Obstet Gynaecol Res,2018,44(11)∶2053-2058.
[11] Kim B,Park Y,Kim B,et al.Diagnostic performance of CA 125,HE4,and risk of Ovarian Malignancy Algorithm for ovarian cancer[J].J Clin Lab Anal,2019,33(1)∶e22624.
[12] Dodge JE,Covens AL,Lacchetti C,et al.Preoperative identification of a suspicious adnexal mass:a systematic review and meta-analysis [J].Gynecol Oncol,2012,126(1)∶157-166.
[13] Zhao T,Hu W.CA125 and HE4:measurement tools for ovarian cancer [J].Gynecol Obstet Invest,2016,81(5)∶430-435.
[14] Shen Y,Li L.Serum HE4 superior to CA125 in predicting poorer surgical outcome of epithelial ovarian cancer [J].Tumor Biol,2016,37(11)∶14765-14772.
[15] Dayyani F,Uhlig S,Colson B,et al.Diagnostic performance of risk of ovarian malignancy algorithm against CA125 and HE4 in connection with ovarian cancer:a meta-analysis[J].Int J Gynecol Cancer,2016,26(9)∶1586-1593.
[16] Sagidain L,Lavie O,Auslander R,et al.CEA in evaluation of adnexal mass:retrospective cohort analysis and review of the literature[J].Int J Biol Markers,2015,30(4)∶e394-e400.
[17] Sagidain L,Lavie O,Auslander R,et al.CA 19-9 in evaluation of adnexal mass:retrospective cohort analysis and review of the literature[J].Int J Biol Markers,2015,30(3)∶e333-e340.
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[19] Sharma JB,Sharma S,Usha BR,et al.A cross-sectional study of tumor markers during normal and high-risk pregnancies [J].Int J Gynaecol Obstet,2015,129(3)∶203-206.
[20] Akinlade F,Cowans NJ,Kisanga MC,et al.Maternal serum CA 19-9 and CA 15-3 levels in pregnancies affected by trisomy 21 [J].Prenat Diagn,2012,32(7)∶644-648.
[21] Timur H,Tokmak A,Yucel A,et al.Diagnostic value of CA 19-9 in pregnancies complicated by spinal neural tube defects:A preliminary study[J].Ginekol Pol,2016,87(12)∶808-813.
[22] Gaccioli F,Aye ILMH,Sovio U,et al.Screening for fetal growth restriction using fetal biometry combined with maternal biomarkers[J].Am J of Obstet Gynecol,2018,218(2)∶725-737.
[23] Bartkute K,Balsyte D,Wisser J,et al.Pregnancy outcomes regarding maternal serum AFP value in second trimester screening[J].J Perinat Med,2017,45(7)∶817-820.
[24] Long W,Zhou Q,Wang H,et al.Second-trimester maternal serum screening biomarkers in the risk assessment for preeclampsia [J].Ann Clin Lab Sci,2018,48(3)∶308-313.
[25] Makris GM,Fotiou A,Chrelias G,et al.Giving birth after fertility sparing treatment for a yolk sac tumour:case report[J].J Clin Diagn Res,2017,11(8)∶QD12-QD13.
[26] 郑媛媛,刘晓巍.妊娠合并卵巢恶性肿瘤诊治进展[J].中国临床医生杂志,2017,45(4)∶18-21.
[27] Elit L,Bocking A,Kenyon C,et al.An endodermal sinus tumor diagnosed in pregnancy:case report and review of the literature [J].Gynecol Oncol,1999,72(1)∶123.
[28] Cole LA,Khanlian SA,Riley JM,et al.Hyperglycosylated hCG ingestational implantation and in choriocarcinoma and testicular germ cell malignancy tumorigenesis [J].J Reprod Med,2006,51(11)∶919-925.
[29] Cole LA.Hyperglycosylated hCG,a review[J].Placenta,2010,31(8)∶653-664.
[30] Li D,Wen X,Ghali L,et al.hCGβ expression by cervical squamous carcinoma-in vivo histological association with tumor invasion and apoptosis[J].Histopathology,2008,53(2)∶147-155.
[31] Hepner A,Negrini D,Hase EA,et al.Cancer during pregnancy:the oncologist overview[J].World J Oncol,2019,10(1)∶28-34.
[32] Luisi S,Florio P,Reis FM,et al.Inhibins in female and male reproductive physiology:role in gametogenesis,conception,implantation and early pregnancy[J].Hum Reprod Update,2005,11(2)∶123-135.
[33] Broumand F,Lak SS,Nemati F,et al.A study of the diagnostic value of Inhibin A Tests for occurrence of preeclampsia in pregnant women [J].Electron Physician,2018,10(1)∶6186-6192.
[34] Petraglia F,Luisi S,Benedetto C,et al.Changes of dimeric inhibin B levels in maternal serum throughout healthy gestation and in women with gestational diseases[J].J Clin Endocrinol Metab,1997,82(9)∶2991-2995.
[35] Fowler PA,Evans LW,Groome NP,et al.A longitudinal study of maternal serum inhibin-A,inhibin-B,activin-A,activin-AB,pro-alphaC and follistatin during pregnancy [J].Hum Reprod,1998,13(12)∶3530-3536.
[36] Wallace EM,Riley SC,Crossley JA,et al.Dimeric inhibins in amniotic fluid,maternal serum,and fetal serum in human pregnancy[J].J Clin Endocrinol Metab,1997,82(1)∶218-222.
[37] Mccredie S,Ledger W,Venetis CA.Anti-Müllerian hormone kinetics in pregnancy and post-partum:a systematic review [J].Reprod Biomed Online,2017,34(5)∶522-533.
[38] Li HW,Hui PW,Tang MH,et al.Maternal serum anti-Mullerian hormone level is not superior to chronological age in predicting Down syndrome pregnancies[J].Prenat Diagn,2010,30(4)∶320-324.
[39] Erin A,Michiko K,Mayu Y,et al.Feto-maternal outcomes of pregnancy complicated by epithelial ovarian cancer:a systematic review of literature[J].Eur J Obstet Gynecol Repro Biol,2015,186∶97-105.
[40] Kodama M,Grubbs BH,Blake EA,et al.Feto-maternal outcomes of pregnancy complicated by ovarian malignant germ cell tumor:a systematic review of literature[J].Eur J Obstet Gynecol Repro Biol,2014,181∶145-156.
[41] Blake EA,Carter CM,Kashani BN,et al.Feto-maternal outcomes of pregnancy complicated by ovarian sex-cord stromal tumor:a systematic review of literature[J].Eur J Obstet Gynecol Repro Biol,2014,175∶1-7.
[2] Mukhopadhyay A,Shinde A,Naik R.Ovarian cysts and cancer in pregnancy[J].Best Pract Res Clin Obstet Gynaecol,2016,33 ∶58-72.
[3] Aslam N,Ong C,Woelfer B,et al.Serum CA125 at 11-14 weeks of gestation in women with morphologically normal ovaries[J].BJOG,2000,107(5)∶689-690.
[4] Han SN,Lotgerink A,Gziri MM,et al.Physiologic variations of serum tumor markers in gynecological malignancies during pregnancy:a systematic review[J].BMC Med,2012,10(1)∶1-10.
[5] Sarandakou A,Protonotariou E,Rizos D.Tumor markers in biological fluids associated with pregnancy[J].Crit Rev Clin Lab Sci,2007,44(2)∶151-178.
[6] Bon GG,Kenemans P,Verstraeten AA,et al.Maternal serum Ca125 and Ca15-3 antigen levels in normal and pathological pregnancy.[J].Fetal Diagn Ther,2001,16(3)∶166-172.
[7] Amampai R,Suprasert P.Cancer antigen 125 during pregnancy in women without ovarian tumor is not often rising[J].Obstet Gynecol Int,2018 ∶8141583.
[8] Lu J,Zheng Z,Zhang Q,et al.Measurement of HE4 and CA125 and establishment of reference intervals for the ROMA index in the sera of pregnant women[J].J Clin Lab Anal,2018,32(5)∶e22368.
[9] Moore RG,Miller MC,Eklund EE,et al.Serum levels of the ovarian cancer biomarker HE4 are decreased in pregnancy and increase with age[J].Am J Obstet Gynecol,2012,206(4)∶349.e1-e7.
[10] Wang Z,Zhou F,Xiao X,et al.Serum levels of human epididymis protein 4 are more stable than cancer antigen 125 in early and mid-term pregnancy[J].J Obstet Gynaecol Res,2018,44(11)∶2053-2058.
[11] Kim B,Park Y,Kim B,et al.Diagnostic performance of CA 125,HE4,and risk of Ovarian Malignancy Algorithm for ovarian cancer[J].J Clin Lab Anal,2019,33(1)∶e22624.
[12] Dodge JE,Covens AL,Lacchetti C,et al.Preoperative identification of a suspicious adnexal mass:a systematic review and meta-analysis [J].Gynecol Oncol,2012,126(1)∶157-166.
[13] Zhao T,Hu W.CA125 and HE4:measurement tools for ovarian cancer [J].Gynecol Obstet Invest,2016,81(5)∶430-435.
[14] Shen Y,Li L.Serum HE4 superior to CA125 in predicting poorer surgical outcome of epithelial ovarian cancer [J].Tumor Biol,2016,37(11)∶14765-14772.
[15] Dayyani F,Uhlig S,Colson B,et al.Diagnostic performance of risk of ovarian malignancy algorithm against CA125 and HE4 in connection with ovarian cancer:a meta-analysis[J].Int J Gynecol Cancer,2016,26(9)∶1586-1593.
[16] Sagidain L,Lavie O,Auslander R,et al.CEA in evaluation of adnexal mass:retrospective cohort analysis and review of the literature[J].Int J Biol Markers,2015,30(4)∶e394-e400.
[17] Sagidain L,Lavie O,Auslander R,et al.CA 19-9 in evaluation of adnexal mass:retrospective cohort analysis and review of the literature[J].Int J Biol Markers,2015,30(3)∶e333-e340.
[18] Cho HY,Kim K,Jeon YT,et al.CA19-9 elevation in ovarian mature cystic teratoma:discrimination from ovarian cancer-CA19-9 level in teratoma[J].Med Sci Monit,2013,19(7)∶230-235.
[19] Sharma JB,Sharma S,Usha BR,et al.A cross-sectional study of tumor markers during normal and high-risk pregnancies [J].Int J Gynaecol Obstet,2015,129(3)∶203-206.
[20] Akinlade F,Cowans NJ,Kisanga MC,et al.Maternal serum CA 19-9 and CA 15-3 levels in pregnancies affected by trisomy 21 [J].Prenat Diagn,2012,32(7)∶644-648.
[21] Timur H,Tokmak A,Yucel A,et al.Diagnostic value of CA 19-9 in pregnancies complicated by spinal neural tube defects:A preliminary study[J].Ginekol Pol,2016,87(12)∶808-813.
[22] Gaccioli F,Aye ILMH,Sovio U,et al.Screening for fetal growth restriction using fetal biometry combined with maternal biomarkers[J].Am J of Obstet Gynecol,2018,218(2)∶725-737.
[23] Bartkute K,Balsyte D,Wisser J,et al.Pregnancy outcomes regarding maternal serum AFP value in second trimester screening[J].J Perinat Med,2017,45(7)∶817-820.
[24] Long W,Zhou Q,Wang H,et al.Second-trimester maternal serum screening biomarkers in the risk assessment for preeclampsia [J].Ann Clin Lab Sci,2018,48(3)∶308-313.
[25] Makris GM,Fotiou A,Chrelias G,et al.Giving birth after fertility sparing treatment for a yolk sac tumour:case report[J].J Clin Diagn Res,2017,11(8)∶QD12-QD13.
[26] 郑媛媛,刘晓巍.妊娠合并卵巢恶性肿瘤诊治进展[J].中国临床医生杂志,2017,45(4)∶18-21.
[27] Elit L,Bocking A,Kenyon C,et al.An endodermal sinus tumor diagnosed in pregnancy:case report and review of the literature [J].Gynecol Oncol,1999,72(1)∶123.
[28] Cole LA,Khanlian SA,Riley JM,et al.Hyperglycosylated hCG ingestational implantation and in choriocarcinoma and testicular germ cell malignancy tumorigenesis [J].J Reprod Med,2006,51(11)∶919-925.
[29] Cole LA.Hyperglycosylated hCG,a review[J].Placenta,2010,31(8)∶653-664.
[30] Li D,Wen X,Ghali L,et al.hCGβ expression by cervical squamous carcinoma-in vivo histological association with tumor invasion and apoptosis[J].Histopathology,2008,53(2)∶147-155.
[31] Hepner A,Negrini D,Hase EA,et al.Cancer during pregnancy:the oncologist overview[J].World J Oncol,2019,10(1)∶28-34.
[32] Luisi S,Florio P,Reis FM,et al.Inhibins in female and male reproductive physiology:role in gametogenesis,conception,implantation and early pregnancy[J].Hum Reprod Update,2005,11(2)∶123-135.
[33] Broumand F,Lak SS,Nemati F,et al.A study of the diagnostic value of Inhibin A Tests for occurrence of preeclampsia in pregnant women [J].Electron Physician,2018,10(1)∶6186-6192.
[34] Petraglia F,Luisi S,Benedetto C,et al.Changes of dimeric inhibin B levels in maternal serum throughout healthy gestation and in women with gestational diseases[J].J Clin Endocrinol Metab,1997,82(9)∶2991-2995.
[35] Fowler PA,Evans LW,Groome NP,et al.A longitudinal study of maternal serum inhibin-A,inhibin-B,activin-A,activin-AB,pro-alphaC and follistatin during pregnancy [J].Hum Reprod,1998,13(12)∶3530-3536.
[36] Wallace EM,Riley SC,Crossley JA,et al.Dimeric inhibins in amniotic fluid,maternal serum,and fetal serum in human pregnancy[J].J Clin Endocrinol Metab,1997,82(1)∶218-222.
[37] Mccredie S,Ledger W,Venetis CA.Anti-Müllerian hormone kinetics in pregnancy and post-partum:a systematic review [J].Reprod Biomed Online,2017,34(5)∶522-533.
[38] Li HW,Hui PW,Tang MH,et al.Maternal serum anti-Mullerian hormone level is not superior to chronological age in predicting Down syndrome pregnancies[J].Prenat Diagn,2010,30(4)∶320-324.
[39] Erin A,Michiko K,Mayu Y,et al.Feto-maternal outcomes of pregnancy complicated by epithelial ovarian cancer:a systematic review of literature[J].Eur J Obstet Gynecol Repro Biol,2015,186∶97-105.
[40] Kodama M,Grubbs BH,Blake EA,et al.Feto-maternal outcomes of pregnancy complicated by ovarian malignant germ cell tumor:a systematic review of literature[J].Eur J Obstet Gynecol Repro Biol,2014,181∶145-156.
[41] Blake EA,Carter CM,Kashani BN,et al.Feto-maternal outcomes of pregnancy complicated by ovarian sex-cord stromal tumor:a systematic review of literature[J].Eur J Obstet Gynecol Repro Biol,2014,175∶1-7.