Angiogenin and MMP-2 as potential biomarkers in the differential diagnosis of gestational trophoblastic diseases

Medicine (Baltimore). 2022 Feb 4;101(5):e28768. doi: 10.1097/MD.0000000000028768.

Abstract

Background: Gestational trophoblastic diseases (GTDs) are characterized by vascular abnormalities of the trophoblast, but their pathogenesis is unknown. Angiogenin (ANG) and matrix metalloproteinase (MMP)-2, which are molecules implicated in the angiogenic process, may play some role in this process.

Material and methods: We determined ANG and MMP-2 in the placental tissues of 26 patients who had a benign mole (BM), 12 patients with gestational trophoblast neoplasia (GTN) (1 invasive hydatidiform mole, 10 choriocarcinomas, and 1 placental-site trophoblastic tumor), and 28 normal chorionic villi (NCV) subjects using immunohistochemistry staining. We obtained the serum samples from 20 patients with GTDs and 20 early pregnant women and evaluated them by the enzyme linked immunosorbent assay.

Results: ANG expression in GTN (66.7%) and BM (100%) samples were both significantly higher (strong/intermediate staining) than in NCV (60.7%) samples (P < .001). Similarly, the immunoreactivities of MMP-2 in the GTN (66.7%) and BM (80.8%) samples were significantly elevated compared to that of the NCV (57.1%) samples (P < .001). The levels of ANG and MMP-2 in the maternal serum of the GTN group were both significantly higher than those of the control group (P < .001). ANG and MMP-2 expressions were associated with gestation age, clinical stage, and FIGO stage. A positive correlation between ANG and MMP-2 expression was observed (rs = 0.725; P < .01).

Conclusion: ANG and MMP-2 levels were significantly elevated in the placental tissues and maternal serum from patients with GTDs. Further studies with more patients may clarify the vascular abnormalities in GTDs and determine potential biomarkers in the differential diagnosis of GTDs.

MeSH terms

  • Biomarkers
  • Diagnosis, Differential
  • Female
  • Gestational Trophoblastic Disease* / diagnosis
  • Humans
  • Hydatidiform Mole* / diagnosis
  • Matrix Metalloproteinase 2 / metabolism*
  • Placenta / metabolism
  • Pregnancy
  • Ribonuclease, Pancreatic / metabolism*
  • Uterine Neoplasms* / diagnosis

Substances

  • Biomarkers
  • angiogenin
  • Ribonuclease, Pancreatic
  • MMP2 protein, human
  • Matrix Metalloproteinase 2