Placental growth factor: a promising diagnostic biomarker for tubal ectopic pregnancy.
BACKGROUND
Tubal ectopic pregnancy is common, but accurate diagnosis is difficult and costly. There is currently no serum test to differentiate tubal from intrauterine implantation, and an effective biomarker of ectopic pregnancy would be a major clinical advance.


OBJECTIVE
A key feature of successful intrauterine implantation is the establishment of a supportive vascular network, and this has been associated with the activity of placental growth factor (PIGF). We hypothesized that the local decidual environment facilitates PIGF-dependent angiogenesis and that this pathway is not active in tubal implantation. We aimed to determine whether tubal implantation is manifest by an attenuation of the normal trophoblast PIGF response and whether serum PIGF levels are different in ectopic compared with intrauterine pregnancy.


METHODS
Tissue and serum analysis was done at a large United Kingdom teaching hospital.


METHODS
Tissue and sera were collected from gestation-matched pregnant women undergoing surgical termination of pregnancy (viable intrauterine) (n = 15), evacuation of uterus for embryonic missed miscarriage (nonviable intrauterine) (n = 10) and surgery for tubal ectopic pregnancy (n = 15).


METHODS
Trophoblast was examined by immunohistochemistry and quantitative RT-PCR, and serum was analyzed by ELISA.


RESULTS
PIGF was localized to the cytotrophoblast cells. Expression of PIGF mRNA was reduced in trophoblast isolated from women with ectopic compared with intrauterine pregnancies (P < 0.05). Serum PIGF was undetectable in women with tubal ectopic pregnancies and reduced, or undetectable, in miscarriage compared with viable intrauterine pregnancies (P < 0.01).


CONCLUSIONS
Serum PIGF is a promising novel diagnostic biomarker for early pregnancy location and outcome, and large-scale studies are now required to determine its clinical utility.
Centre for Reproductive Biology, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom. andrew.horne@ed.ac.uk
Andrew W
AW
Horne
Julie L V
JL
Shaw
Amanda
A
Murdoch
Sarah E
SE
McDonald
Alistair R
AR
Williams
Henry N
HN
Jabbour
W Colin
WC
Duncan
Hilary O D
HO
Critchley
D000704:Analysis of Variance; D015415:Biomarkers / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D010920:Placenta / Q000378:metabolism*; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D011274:Pregnancy, Tubal / Q000175:diagnosis* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000378:metabolism*
D015415:Biomarkers; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D000072483:Placenta Growth Factor