Expression characteristics and diagnostic value of angiogenic molecules in intravenous leiomyomatosis

Abstract

Objective: This study aims to analyze the clinicopathological characteristics of patients with intravenous leiomyoma (IVL), and to explore the expression characteristics and diagnostic value of angiogenesis related molecules in IVL. Methods: The clinicopathological data of 40 patients with IVL at Women's Hospital, School of Medicine, Zhejiang University from January 2013 to April 2021 were reviewed. Log-rank test was performed to compare the difference in recurrence-free survival (RFS) rates among patients with different clinicopathological characteristics. Immunohistochemistry (IHC) staining was performed on 10 angiogenesis related molecules to analyze their expression characteristics in IVL. The sensitivity and specificity of molecules with high expression rates in the diagnosis of IVL were calculated, the receiver operating characteristic curve (ROC) was plotted and the area under ROC (AUC) was calculated to evaluate the diagnostic value. Results: Median age of the 40 patients was 47 (43, 50) years. The clinical manifestations of IVL were atypical with the diagnostic accuracy of preoperative ultrasound was 12.5% (5/40), CT and/or MRI was 26.7% (8/30), and intraoperative frozen section was 30.0% (12/40). The overall recurrence rate of IVL was 10.0% (4/40). The Log-rank test showed that the cumulative recurrence-free survival rate of IVL patients with previous cesarean section (40.9%) was lower than that of those without cesarean section (96.4%) (P<0.05); and their median RFS time was shorter than those without cesarean section (16.4 months vs 22.2 months). The overall positive rates of adrenomedullin (ADM), fibroblast growth factor receptor 1 (FGFR1), vascular endothelial growth factor receptor 3 (VEGFR3) and angiogenin receptor tyrosine kinase receptor 1 (TIE1) were 65.0% (26/40), 75.0% (30/40), 57.5% (23/40) and 50.0% (20/40), respectively. FGFR1 expression intensity and positive rate were higher in tumors with a maximum diameter greater than 5 cm than in tumors with a maximum diameter smaller than 5 cm (P<0.05). The AUC of FGFR1 combined with ADM, VEGFR3, and TIE1 was 0.876 (95%CI: 0.788-0.964, P<0.001). Conclusions: There was no typical clinical manifestation of IVL. A history of the previous cesarean section indicated a lower cumulative recurrence-free survival rate and shorter recurrence interval. It was hard to diagnose IVL by sonography, radiography, or frozen section pathology. FGFR1, ADM, VEGFR3, and TIE1 were all highly expressed in IVL, and the efficacy of the combination of the four molecules in diagnosing IVL was higher than that of imaging and classical vascular endothelial markers, which are expected to be promising molecular diagnostic markers.