VEGF和β-HCG与输卵管妊娠滋养细胞侵入管壁深度的关联性研究
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摘要
目的评估输卵管壶腹部妊娠患者滋养细胞浸润输卵管壁深度与血管内皮生长因子(VEGF)及β-人绒毛膜促性腺激素(β-HCG)血清浓度之间的关联性。方法选择输卵管壶腹部妊娠且已行患侧输卵管切除术患者80例。手术当天检测血清VEGF和β-HCG浓度。血清VEGF含量的测定采用ELISA法。留取切除的患侧输卵管及妊娠组织,输卵管肌纤维用Masson染色,滋养细胞用人胎盘催乳素(HPL)免疫组织化学染色。依据术后病理结果中滋养细胞浸入输卵管壁的深度,将80例患者分为Ⅰ~Ⅲ期。血清β-HCG采用双抗体夹心光化学测定法。结果Ⅰ期血清VEGF和β-HCG浓度的平均值明显低于Ⅱ期,而Ⅱ期明显低于Ⅲ期(P<0.05)。Ⅰ期和Ⅱ期临界值VEGF浓度为308.6 ng/L,敏感度100.0%,特异度92.6%,Ⅱ期和Ⅲ期临界值VEGF浓度为431.9 ng/L,敏感度79.3%,特异度79.2%;Ⅰ期和Ⅱ期临界值β-HCG浓度为2 509.6 IU/L,敏感度91.7%,特异度81.5%,Ⅱ期和Ⅲ期临界值β-HCG浓度为13 142.6 IU/L,敏感度72.4%,特异度95.8%。结论输卵管妊娠患者血清中的VEGF和β-HCG浓度与滋养细胞浸润输卵管壁深度有关,可作为妊娠滋养细胞浸润输卵管管壁深度组织学分期的评估指标。
Objective To assess the association between the depth of trophoblastic penetration into the tubal wall withserum concentrations of vascular endothelial growth factor(VEGF) and β-human chorionic gonadotropin(β-HCG). Methods Eighty patients with a diagnosis of tubal pregnancy in the ampullary region underwent radical surgical treatment(sal-pingectomy),were included in this study. The serum levels of VEGF and β-HCG were detected on the day of surgery. The se-rum level of VEGF was measured by ELISA. The serum level of β-HCG was quantified with a two-site immunofluorimetricassay based on the direct sandwichtechnique. Histological material was stained with Masson′s trichrome to identify muscularfibers. Immunohistochemical staining was used for human placental lactogen(h PL) to identify intermediate trophoblast anddetermine the depth of trophoblastic invasion into the tubal wall. The ampullary pregnancies were classified histologically ac-cording to the depth of trophoblastic infiltration into the tubal wall. Results The mean serum values of VEGF and β-HCG were significantly lower in patients with stage I tubal infiltration than those of stage Ⅱ,and which were significantly lower inpatients with stage Ⅱ than those in stage Ⅲ(P<0.05). The threshold serum value of VEGF was 308.6 ng/L,the sensitivitywas 100.0% and the specificity was 92.6% for stageⅠand stage Ⅱ. The threshold serum value of VEGF was 431.9 ng/L,thesensitivity was 79.3% and specificity was 79.2% for stage Ⅱ and Ⅲ. The threshold serum value of β-h CG was 2 509.6 IU/L,the sensitivity was 91.7% and specificity was 81.5% for stageⅠ and stage Ⅱ,and levels of 13 142.6 IU/L,72.4% and 95.8%for stage Ⅱ and stage Ⅲ. Conclusion The depth of trophoblastic penetration into the tubal wall is associated with maternalserum concentrations of VEGF and β-HCG,which can be used as the evaluation index for histological staging of trophoblas-tic tissue infiltration.
Objective To assess the association between the depth of trophoblastic penetration into the tubal wall withserum concentrations of vascular endothelial growth factor(VEGF) and β-human chorionic gonadotropin(β-HCG). Methods Eighty patients with a diagnosis of tubal pregnancy in the ampullary region underwent radical surgical treatment(sal-pingectomy),were included in this study. The serum levels of VEGF and β-HCG were detected on the day of surgery. The se-rum level of VEGF was measured by ELISA. The serum level of β-HCG was quantified with a two-site immunofluorimetricassay based on the direct sandwichtechnique. Histological material was stained with Masson′s trichrome to identify muscularfibers. Immunohistochemical staining was used for human placental lactogen(h PL) to identify intermediate trophoblast anddetermine the depth of trophoblastic invasion into the tubal wall. The ampullary pregnancies were classified histologically ac-cording to the depth of trophoblastic infiltration into the tubal wall. Results The mean serum values of VEGF and β-HCG were significantly lower in patients with stage I tubal infiltration than those of stage Ⅱ,and which were significantly lower inpatients with stage Ⅱ than those in stage Ⅲ(P<0.05). The threshold serum value of VEGF was 308.6 ng/L,the sensitivitywas 100.0% and the specificity was 92.6% for stageⅠand stage Ⅱ. The threshold serum value of VEGF was 431.9 ng/L,thesensitivity was 79.3% and specificity was 79.2% for stage Ⅱ and Ⅲ. The threshold serum value of β-h CG was 2 509.6 IU/L,the sensitivity was 91.7% and specificity was 81.5% for stageⅠ and stage Ⅱ,and levels of 13 142.6 IU/L,72.4% and 95.8%for stage Ⅱ and stage Ⅲ. Conclusion The depth of trophoblastic penetration into the tubal wall is associated with maternalserum concentrations of VEGF and β-HCG,which can be used as the evaluation index for histological staging of trophoblas-tic tissue infiltration.
引文
[1]Farquhar CM.Ectopic pregnancy[J].Lancet,2005,366:583-591.
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[3]Ali A A,Abdallah TM,Siddig MF.Diagnosis of ruptured ectopicpregnancy is still a challenge in eastern Sudan[J].Aft J ReprodHealth,2011,15(4):106-108.
[4]Wang JL.Clinical Epidemiology[M].Beijing:People′s Health Press,2001:65-69.[王家良.临床流行病学[M].北京:人民卫生出版社,2001:65-69].
[5]Butler SA,Abban TK,Borrelli PT,et al.Single point biochemicalmeasurement algorithm for early diagnosis of ectopic pregnancy[J].Clini Biochem,2013,46(13-14):1257-1263.doi:10.1016/j.clin-biochem.2013.06.019.
[6]Shifren JL,Tseng JF,Zaloudek CJ,et al.Ovarian steroid regulationof vascular endothelial growth factor in the human endometrium:im-plications for angiogenesis during the menstrual cycle and in thepathogenesis of endometriosis[J].J Clin Endocrinol Metab,1996,81(8):3112-3118.
[7]Botros R,Candice PH,Mostafa A.Challenges in the diagnosis andmanagement of interstitial and comual ectopic pregnancies[J].Mid-dle East Fertil Soc J,2013,18(4):235-240.doi:10.1016/j.ejogrb.2014.04.029.
[8]Rausch ME,Beer L,Sammel MD,et al.A disintegrin and metallo-protease protein-12 as a novel marker for the diagnosis of ectopicpregnancy[J].Fertil Steril,2011,95(4):1373-1378.doi:10.1016/j.fertnstert.2010.12.040.
[9]Cabar FR,Pereira PP,Schultz R,et al.Predictive factors of tropho-blastic invasion into the ampullary region of the tubal wall in ecto-pic pregnancy[J].Hum Reprod,2006,21:2426-2431.doi:10.1007/s00404-012-2566-1.
[10]Juneau C,Bates GW.Reproductive outcomes after medical and sur-gical management of ectopic pregnancy[J].Clin Obstet Gynecol,2012,55(2):455-460.doi:10.1097/GRF.0b013e3182510a88.
[11]Pereira PP,Cabar FR,Schultz R,et al.Association between ultra-sound findings and extent of trophoblastic invasion into the tubalwall in ampullary pregnancy[J].Ultrasound Obstet Gynecol,2009,33:472-476.doi:10.1002/uog.6333.
[12]Gao HJ,Dai XJ,Wang HX,et al.Angiogenic factor VEGF and itsreceptor regulating normal pregnancy and abortion Placenta in Rhe-sus[J].Chinese Journal of Family Planning,2005,13:356-359.[高红军,代解杰,王红星,等.血管新生调节因子VEGF及其受体在恒河猴正常妊娠和药物流产胎盘中的表达[J].中国计划生育学杂志,2005,13:356-359].doi:10.3724/SP.J.1206.2005.00095.
[13]Wan H,Liu HW,Xi N.Tamoxifen combined with mifepristone med-ical abortion on early pregnancy villi VEGF and TGF beta 1 expres-sion effect[J].Reproduction&Contraception,2007,27:198-203.[万虹,刘宏伟,席娜.三苯氧胺联合米非司酮药物流产对早孕绒毛VEGF、TGF-β1表达的影响[J].生殖与避孕,2007,27:198-203].doi:0253-357X(2007)03-0198-06.
[2]Natale A,Candiani M,Merlo D,et al.Human chorionic gonado-trpin level as a predictor of trophoblastic infiltration into the tubalwall in ectopic pregnancy:a blind study[J].Fertile Steril,2003,79:981-986.
[3]Ali A A,Abdallah TM,Siddig MF.Diagnosis of ruptured ectopicpregnancy is still a challenge in eastern Sudan[J].Aft J ReprodHealth,2011,15(4):106-108.
[4]Wang JL.Clinical Epidemiology[M].Beijing:People′s Health Press,2001:65-69.[王家良.临床流行病学[M].北京:人民卫生出版社,2001:65-69].
[5]Butler SA,Abban TK,Borrelli PT,et al.Single point biochemicalmeasurement algorithm for early diagnosis of ectopic pregnancy[J].Clini Biochem,2013,46(13-14):1257-1263.doi:10.1016/j.clin-biochem.2013.06.019.
[6]Shifren JL,Tseng JF,Zaloudek CJ,et al.Ovarian steroid regulationof vascular endothelial growth factor in the human endometrium:im-plications for angiogenesis during the menstrual cycle and in thepathogenesis of endometriosis[J].J Clin Endocrinol Metab,1996,81(8):3112-3118.
[7]Botros R,Candice PH,Mostafa A.Challenges in the diagnosis andmanagement of interstitial and comual ectopic pregnancies[J].Mid-dle East Fertil Soc J,2013,18(4):235-240.doi:10.1016/j.ejogrb.2014.04.029.
[8]Rausch ME,Beer L,Sammel MD,et al.A disintegrin and metallo-protease protein-12 as a novel marker for the diagnosis of ectopicpregnancy[J].Fertil Steril,2011,95(4):1373-1378.doi:10.1016/j.fertnstert.2010.12.040.
[9]Cabar FR,Pereira PP,Schultz R,et al.Predictive factors of tropho-blastic invasion into the ampullary region of the tubal wall in ecto-pic pregnancy[J].Hum Reprod,2006,21:2426-2431.doi:10.1007/s00404-012-2566-1.
[10]Juneau C,Bates GW.Reproductive outcomes after medical and sur-gical management of ectopic pregnancy[J].Clin Obstet Gynecol,2012,55(2):455-460.doi:10.1097/GRF.0b013e3182510a88.
[11]Pereira PP,Cabar FR,Schultz R,et al.Association between ultra-sound findings and extent of trophoblastic invasion into the tubalwall in ampullary pregnancy[J].Ultrasound Obstet Gynecol,2009,33:472-476.doi:10.1002/uog.6333.
[12]Gao HJ,Dai XJ,Wang HX,et al.Angiogenic factor VEGF and itsreceptor regulating normal pregnancy and abortion Placenta in Rhe-sus[J].Chinese Journal of Family Planning,2005,13:356-359.[高红军,代解杰,王红星,等.血管新生调节因子VEGF及其受体在恒河猴正常妊娠和药物流产胎盘中的表达[J].中国计划生育学杂志,2005,13:356-359].doi:10.3724/SP.J.1206.2005.00095.
[13]Wan H,Liu HW,Xi N.Tamoxifen combined with mifepristone med-ical abortion on early pregnancy villi VEGF and TGF beta 1 expres-sion effect[J].Reproduction&Contraception,2007,27:198-203.[万虹,刘宏伟,席娜.三苯氧胺联合米非司酮药物流产对早孕绒毛VEGF、TGF-β1表达的影响[J].生殖与避孕,2007,27:198-203].doi:0253-357X(2007)03-0198-06.