具有复杂遗传学特征的双胎妊娠产物分子病理诊断

Molecular pathological diagnosis of twin pregnancy with complicated genetical characteristics

目的联合p57染色和短串联重复(STR)基因分型,探讨具有复杂遗传学特征的双胎妊娠的分子病理诊断思路。方法收集2015—2019年北京大学第三医院组织形态学特征提示葡萄胎的双胎妊娠10例患者资料,采用EnVision法行p57免疫组织化学染色,PCR-毛细管电泳法检测STR基因分型。结果患者年龄23~36岁,平均29.5岁,其中7例为接受人工辅助生殖技术而受孕。免疫组织化学染色结果显示,3例患者的绒毛组织呈"绒毛异质性"p57染色模式,经STR分型确认为伴有完全性葡萄胎的双胎妊娠,其中1例患者确诊为持续性滋养细胞疾病。5例患者的绒毛组织呈p57一致阳性,但STR分型结果为多倍体,提示为双胎妊娠,其中4例在≥40%的基因座显示过量的父源性基因,不能排除伴有部分性葡萄胎。另1例患者所有基因座均显示母源性基因占优势,符合不伴葡萄胎的双胎妊娠。2例p57染色同时表现为"绒毛异质性"和"细胞异质性"的患者,STR分型提示为伴有父源/双亲嵌合体的双胎妊娠。结论正确评估p57染色模式和准确解读STR基因分型结果,可以协助病理医师对具有复杂遗传学特征的双胎妊娠作出明确诊断或满足临床分流策略的倾向性诊断,协助临床制定随访方案。

Objective To investigate the molecular pathological diagnostic strategy of twin pregnancy(TP)with complex genetic characteristics,using p57 immunohistochemistry and short tandem repeat(STR)genotyping.Methods Ten cases of TP with suspected hydatidiform mole(HM)according to pathological morphology were collected in Peking University Third Hospital from 2015 to 2019,and were subject to p57 immunohistochemistry,STR genotyping and follow-up.Results The age of ten patients ranged 23 to 36 years,with an average of 29.5 years.Seven patients accepted assisted reproductive techniques in this conception.Three patients with"divergent"p57 staining pattern were diagnosed as TP with complete HM by STR,in which one had a persistent trophoblastic disease.The villi of five patients were consistently positive for p57,but the genotyping result was polyploid and suspicious as TP.Four of them showed excessive paternal alleles at more than 40%of the loci,suggesting that concomitant partial moles could not be excluded.One patient was diagnosed as TP without HM according to the maternal allelic predominance at all loci in villi.Two patients with p57"divergent"and"discordant"staining villi were genotyped as TP with mosaic conception.Conclusions The correct identification of p57 staining pattern and accurate interpretation of STR genotyping results are important in diagnosing TP.It may assist pathologists in making a definite or likely diagnosis of TP with complex genetic features to fulfill clinical triage strategies and contribute to formulate a reasonable follow-up approach.