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Abstract 479: mRNA in situ expression of candidate genes for progression risk tissue biomarkers, in premalignant cervical lesions uri icon


  • Abstract Background Comparing the in situ differences in mRNA expression of candidate genes between normal cervical tissue and premalignant lesions, could contribute to detect progression risk biomarkers. Use of RNAscope chromogenic in situ hybridization (CISH) that amplifies specific mRNA signals and detects molecules as points that can be quantified, could help the detection of these biomarkers. Methods A tissue microarray was constructed from cervical samples (conization and histerectomy). Representative areas of normal cervix, low-grade (LSIL), and high-grade squamous intraepithelial lesions (HSIL) were chosen. RNAscope 2.5HD Red HPV-HR18 assay that detect E6/E7 mRNA for eighteen high-risk (HR) HPV genotypes, and RNAscope 2.5HD Red assays to detect mRNA from: KRT16, TMEM45A and RBP1, were performed. The stainings were scored by two pathologist from 0 to 4 in a semi-quantitative analysis based on the average number of dots per cell; mean score values were compared using GraphPad Prism 7.0. A p<0.05 was considered statistically significant. Results A total of 390 cervical tissues cores from 169 patients with mean age 36.08 years (SD ±10.48) were included. Mean mRNA expression of HR-HPV E6/E7, TMEM45A and RBP1 were significantly higher in HSIL compared to LSIL and normal cervix squamous epithelium. KRT16 mRNA expression scores in normal cervix squamous epithelium, LSIL, and HSIL, were not significantly different (Table 1). Conclusions CISH allowed to detect E6/E7 mRNA molecules for eighteen HR-HPV genotypes in routinely processed tissues, and to evaluate the expression of the described candidate genes in their context without destroying the tissue morphology. Identification of differential expression between normal cervical tissue and HSIL supports the possible role of TMEM45A and RBP1 in cervical cancer progression and its potential use as progression risk tissue biomarkers. Table 1.Biomarkers candidate genes expression profiles in normal cervix, LSIL and HSILCISH scoresMean (±SD)95% CINormal cervixLSILHSILp valueHR-HPV E6/E7 mRNAn=640.4098(±0.7611)0.2149-0.6048n=640.4098 (±0.7611)0.2149-0.6048n=1381.294 (±1.189)1.078-1.51<0.0001*TMEM45A mRNAn=761.105 (± 1.322)0.8031-1.407n=691.232 (±1.477)0.8771-1.587n=2381.514(± 1.491)1.264-1.7650.046*RBP1 mRNAn=660.4242(±0.7658)0.236-0.6125n=740.5135 (±0.9826)0.2859-1.159n=1301.3 (±1.186)1.094-1.506<0.0001*KRT16 mRNAn=840.9524(±1.15)0.7028-1.202n=770.8831 (±1.214)0.6076-1.159n=1571.115 (±1.41)0.8924-1.3370.573* Citation Format: Ines Benedetti, Felipe Ruiz, Reinhard Rodríguez. mRNA in situ expression of candidate genes for progression risk tissue biomarkers, in premalignant cervical lesions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 479.