Supplementary Material for: Possible Association between Cathepsin V and the Development of Placenta Accreta Spectrum Disorders

Background/Aims: The study aimed to evaluate molecular changes related to trophoblast adhesion in placenta accreta spectrum (PAS) disorders. Methods: A retrospective analysis of 10 PAS cases in which both the trophoblast adherent site and the non-adherent site were identified was performed in April 2010 and March 2013. Microarray analysis and reverse transcription polymerase chain reaction (RT-PCR) analyses were performed to extract upregulated genes in the adherent site. Gene expression changes were examined by immunohistochemistry. Results: Microarray analysis showed that 157 transcripts were > 3-fold upregulated, including the following: a disintegrin and metalloproteinase-28 (ADAM28), 3.10-fold; cathepsin V (CTSV), 3.73-fold; cathepsin S (CTSS), 3.46-fold; and matrix metalloproteinase-19 (MMP19), 3.41-fold. RT-PCR showed relatively high mRNA expressions. On immunohistochemistry, extravillous trophoblast (EVT) at the non-adherent site showed weak or no CTSV expression, whereas EVT that invaded myometrium at the adherent site showed strong expression (histological score, median [min-max], 115.6 [37.6–153.6] vs. 184.8 [56.4–222.8], p < 0.05). MMP19 showed moderate staining, with no difference between the adherent and non-adherent sites. ADAM28 and CTSS showed weak or no staining. Discussion: This limited study suggests that CTSV may be involved in the pathogenesis of PAS.