Angiogenin and Gestational Trophoblastic Tumors, a Promising Prognostic Marker

Abstract

The aim of this study was to evaluate the diagnostic and prognostic values of serum angiogenin concentration in cases with gestational trophoblastic diseases (GTDs). Seventy-two patients with GTDs and 20 first trimester healthy pregnant women (controls) participated in this study. According to the WHO scoring system, GTDs were subgrouped into 24 hydatiform mole spontaneous regression (HMSR), 18 postmolar gestational trophoblastic tumors of high risk (PMHR), 16 low-risk choriocarcinoma, and 14 high-risk choriocarcinoma. Before treatment, a blood sample from each case was assayed for human chorionic gonadotrophin , subunit (hCGb) by radioimmunoassay and angiogenin by enzyme immunoassay. Follow-up hCGb and angiogenin assays were carried out for 1 year after treatment. Pretreatment of abnormal values of serum angiogenin (> 711 ng/ml, upper 95% confidence interval of controls) was encountered in 100% of PMHR cases compared to no single case of HMSR. Serum angiogenin levels in low- and high-risk cases with choriocarcinoma were significantly higher than in controls. Abnormal high values were encountered in 25% and 86% of cases, respectively. None of the low-risk cases exceeded 920 ng/ml, while 72% of high-risk cases exceeded this value. Serial angiogenin assays were correlated with disease progression and were positively correlated with serum hCGb (r = 0.75, p < 0.01). In conclusion, serum angiogenin may be a valuable marker of differential diagnosis of GTDs and its serial measurements are suggestive of remission and effective therapeutic intervention or disease progression.

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

“…Moreover, we demonstrated that ANG localized to the villous syncytiotrophoblast cells in GTD placenta tissues and maternal serum similar to that in normal patients by using IHC. Shaarawy et al found that the serum ANG concentration showed diagnostic and prognostic values for the differential diagnosis of GTD, [18] which was consistent with our results.…”

“…[15][16][17] Serum ANG levels in choriocarcinoma cases were significantly higher than in healthy pregnant women. [18] However, its expression in GTN tissues and mechanism remain unknown, as cases are rare. [19] Human placentation processes require a balance between the degradation of the maternal decidual vasculature and the concurrent angiogenesis directed by the developing embryo.…”

“…In many types of tumors, the worse the differentiation of the tumors, the stronger the ANG expression [15–17] . Serum ANG levels in choriocarcinoma cases were significantly higher than in healthy pregnant women [18] . However, its expression in GTN tissues and mechanism remain unknown, as cases are rare [19] …”

Angiogenesis in gynecological oncology-mechanism of tumor progression and therapeutic targets

“…Serum angiogenin level in low‐ and high‐risk patients with choriocarcinoma is significantly higher and correlates with disease progression (79) . Moles and choriocarcinoma show marked elevations of serum IL‐1β, IL‐6, and TNF‐α with disease progression (80) .…”

Molecular and clinical characterization of ANG expression in gliomas and its association with tumor-related immune response

“…Angiogenin (ANG) has been extensively reported across a variety of malignant diseases, including gestational trophoblast neoplasia ( 5 , 6 ), prostate cancer ( 7 , 8 ), bladder cancer ( 9–13 ), nasopharyngeal carcinoma ( 14 , 15 ), colorectal cancer ( 16 , 17 ), hepatocellular carcinoma ( 18 ), pancreatic cancer ( 19 ), renal cell carcinoma ( 20 ), gastric and colon cancer ( 21 ), lung cancer ( 22 , 23 ), breast cancer ( 24 , 25 ), multiple myeloma ( 26 ), lymphoma ( 27 , 28 ), oral cancer ( 29 ), neuroblastoma ( 30 ), melanoma ( 31 ), cervical cancer ( 32 ), and laryngeal carcinoma ( 33 ). ANG, also termed RNase5, belongs to the RNase A superfamily, whose family members primarily play roles in ribonucleolytic activity.…”