Cytotrophoblast alterations in placentas from disorders associated with anti-phospholipid antibodies

Abstract

s / Placenta 35 (2014) A1eA23 A16 using the QIAamp® DNA FFPE Tissue Kit (Qiagen). Bisulfite treatment was followed by MSP. DNA was amplified using the Platinum® Blue (Invitrogen). The expression of Notch1 and Dll1 was detected by IHC using EnVision method. Results: The rates of Dll1 promoter hypermethylation were significantly higher in the early-onset PE group (61.5%; 8/13) than in late-onset PE group (12.0%; 3/25; P<0.001). In addition, their rates were significantly higher in the first trimester miscarriage group (80.0%, 8/10) than in the second trimester stillbirth (6.7%, 1/15; P<0.001). No significant differences in the rates of Notch1 promoter hypermethylation were found among the groups studied. Dll1 and Notch1 are expressed in the cytoplasm of villous trophoblast and decidual cell. In our preliminary study, those proteins expression are not associated with corresponding those methylation status. Conclusions: The epigenetic inactivation of Dll1 is involved in the occurrence of adverse outcome of pregnancy, especially early-onset PE. Dll1 promoter hypermethylation is expected to be a target of molecular diagnosis and treatment of these diseases. O-059. CYTOTROPHOBLAST ALTERATIONS IN PLACENTAS FROM DISORDERS ASSOCIATED WITH ANTI-PHOSPHOLIPID ANTIBODIES Rie Kawaguchi, Akiko Konoshi, Yukiko tanuma, Taizan Kamide, Hiroaki Aoki, Tomohiro Tanemoto, Kuniaki Oura, Aikou Okamot. Department of OB/GYN, Jikei Univ. School of Med., Japan Objectives: Pregnancy pathologies such as preeclampsia, fetal growth restriction and abruption are well known to be affected by an impaired placental development. Antiphospholipid antibodies (APLs) are associated with placental insufficiency by activation of the complement cascade. Here we investigated the effect of APLs and dysregulated clotting factors on the biology of villous trophoblast. Methods: Placentas were collected from a normal control group (NC; n1⁄48, 27-38 gestational weeks), an APL group (n1⁄410, 25-36 weeks), and a NAPS group (n1⁄410, 27-35 weeks), where patients had no APL, but disorders of serum clotting factors. Placentas were stained for anti Ki-67 and anticytokeratin 7 to selectively identify proliferating villous cytotrophoblasts. Images were systematically randomly selected and cytotrophoblasts counted. One way ANOVA and post hoc analysis were applied as statistical analysis. Results: The ratio of Ki-67 positive cytotrophoblasts in NC gradually decreased in accordance with gestational age, while this was not apparent in APS and NAPS. The mean of Ki-67 positive cells was significant reduced in APL (12.1 ±7.1%) and CF (13.3 ±5.8%) compared to NC (22.6 ±6.4%). The total number of cytotrophoblasts was reduced in APS (578 ±209) compared to NAPS (822 ±232) and NC (780 ±149). Conclusion: Throughout the third trimester of pregnancy there are significant differences in cytotrophoblast features such as total number and rate of proliferating cells in patients with APL and a dysregulated clotting system. Although cytotrophoblast proliferation was reduced in all compromised placentas, the total number of cytotrophoblasts only decreased in APS. We suggest that APL promote inhibition of cytotrophoblast proliferation throughout pregnancy, while in the NAPS group, an increasing amount of fibrin depositions finally leads to a decrease in trophoblast proliferation but does not affect total cell count. O-060. CLINICOPATHOLOGICAL ANALYSIS OF A PATIENT WITH CERVICOISTHMIC PREGNANCY: IMPLICATION OF PRECURSOR LESION TO PLACENTA ACCRETE Yosuke Sugita, Koichi Yoneyama, Mirei Yonezawa, Yuka Shirai, Kenichiro Watanabe, Nozomi Ouchi, Yoshimitsu Kuwabara, Toshiyuki Takeshita. Nippon Medical School Hospital Obstetrics &; Gynecology, Japan Cervico-isthmic pregnancy is rare and might be a part of the pathogenesis of placenta accreta. However, this entity of the disease is not widely known and there is no consensus on its management. Here we report a patient with cervico-isthmic pregnancy in a 34-year-old woman with the history of cesarean section delivery. The patient was referred to Nippon Medical School Hospital for suspicion of a cervical pregnancy. Transvaginal ultrasound revealed the gestational sac with the fetal heartbeat located in the cervico-isthmic region adjacent to the prior cesarean delivery scar. We clinically diagnosed it with a cesarean scar pregnancy, and total abdominal hysterectomy was performed. Macroscopically, the gestational sac attached to the posterior wall of the cervico-isthmic region. Histological examination revealed muscle infiltration of the intermediate trophoblast in the cervico-isthmic region. This is an important case showing the possibility of pathogenesis of placenta accreta through a cervico-isthmic pregnancy. O-063. A CASE OF INTRAPLACENTAL CHORIOCARCINOMA IDENTIFIED WHILE SEARCHING FOR THE CAUSE OF FETOMATERNAL HEMORRHAGE Misato Ogino , Kaori Kawakita , Nobuko Yamashita , Nobuyuki Tomura , Rie Sakai , Hitomi Okusugi , Eri Konda , Yumiko Sahara , Yasuhito Takeuchi , Misa Ishihara , Kimio Hashimoto . Department of Obstetrics and Gynecology, Nishikobe medical center, Japan; Department of Pathology, Nishikobe medical center,