Transcriptional activity and alternative splice mRNA forms of Flt-1, Flk-1 genes in the estimation of risk progression of squamous intraepithelial lesions and cervical cancer

So far there have been known two highly specific VEGF receptors that occur in vascular endothelium: Flt-1 (VEGFR-1) and Flk-1/KDR (VEGFR-2) and the soluble form of Flt-1 – sFlt-1. High expression of these receptors was observed in many cancers and as a result of chronic tissue hypoxia. The aim of this study was to evaluate transcriptive activity and forms of alternative splicing of VEGFR-1 and VEGFR-2 genes mRNA and their relationship with the progression of squamous intraepithelial lesions and cervical cancer. Tissue specimens used for molecular analysis were obtained form 119 women. After histological examination they were divided into several morphological groups: control group – 43 specimens of normal cervix, LSIL group – 38 specimens, HSIL group – 17 specimens, RAK group – 21 specimens of squamous cancer in IB-IIB stage. To compare genes expression in specimens different in weight, there was established a common coefficient – a number of copies of mRNA per 1 µg of total mRNA. In LSIL group, the presence of Flt-1 gene mRNA in squamous intraepithelial lesions caused an increase in relative risk of progression (RR=2.26±1.24), whereas, in the same group, this parameter for Flk-1 gene mRNA was RR=2.41±1.13. A fivefold increase in the progression relative risk in HSIL group was shown. In RAK group the progression risk for Flt-1 and Flk-1 genes was RR=8.17±4.25 and RR=4.58±2.1, respectively. The presence of the soluble form sFlt-1 had no effect on the increase in the progression risk in RAK group and had a minimal effect in HSIL group.