ABCB5 Is Expressed by Placental Cytotrophoblasts.
Elgida R Volpicelli, Qian Zhan, David W Kindelberger, Markus H Frank, Natasha Y Frank, Cristopher P Crum, George F Murphy. Brigham and Women's Hospital, Boston, MA; Children's Hospital, Boston, MA
Background: Transport proteins play important roles in regulating exchange across the placental maternal-fetal interface. P-glycoprotein (P-gp) encoded by the MDR1 gene is one of the best characterized ATP-dependent drug efflux transporters in the placenta. P-gps (specifically ABCB1) expressed on the maternal facing border of syncytiotrophoblast microvilli, participate in the efflux of hydrophobic and cationic agents into the maternal blood, reducing chemical exposure to the fetus. ABCB5 [subfamily B (MDR/TAP)] is a novel human ABC transporter encoded on chromosome 7p15.3. ABCB5 is expressed on the plasma membrane of physiologic human skin progenitor cells and chemoresistant melanoma stem cells; functions as a rhodamine efflux transporter and regulates membrane potential and the resultant propensity for cell fusion. ABCB5 expression in trophoblastic cells (both neoplastic and non-neoplastic) has never been described.
Design: ABCB5 immunohistochemistry was performed (as previously described: Nature 451:345-349, 2008) on formalin fixed, paraffin embedded placental tissue from five early pregnancies (< 10 weeks gestational age), 5 term pregnancies, 5 partial moles, and 5 complete moles. Additionally tumor cells from 5 choriocarcinoma, and 5 placental site trophoblastic tumor (PSTT) cases were examined.
Results: Perinuclear and membranous/cytoplasmic ABCB5 staining was observed in villous cytotrophoblasts in 100% (5/5) of first trimester placentas, 0% of term placentas (0/5), 100% of partial moles (5/5) and 100% of complete moles (5/5). Notably, reactivity was discretely restricted to the cytotrophoblast layer, with no staining of overlying syncytiotrophoblast. There was staining in 20% of choriocarcinomas (1/5) and 40% of PSTTs (2/5).
Conclusions: Prior studies have localized expression of MDR-1, ABCB1, within the syncytiotrophoblasts of early placentas. Its function may be protective based on efflux function at the level of cell membranes. Our results show that ABCB5 is preferentially expressed in villous cytotrophoblasts, a stem cell population, which through cell fusion gives rise to syncytiotrophoblasts. Thus, in addition to the coordinated protective efflux function common to ABCB5 and other P-gp transporters at the maternal-fetal interface, ABCB5 may specifically be involved in fusion events inherent in syncytiotrophoblast formation. Studies are presently underway to test this hypothesis both in vitro as well as in the context of human conditions potentially involving defective syncytiotrophoblast formation.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 217, Monday Morning