Abstract 2530: Differences in mRNA expression of a candidate gene, between normal cervical tissue and cervical premalignant lesions
Authors: Ines Benedetti, Reinhard Rodríguez, Lia Barrios
Journal: Cancer Research (2021)

Abstract Background: Cervical cancer is the fourth most common cancer in women worldwide, with around 85% of cases occurring in underdeveloped countries. The diagnosis of premalignant lesions is ​​the objective of cervical cancer prevention programs, aimed at increasing the chances of cure and survival time. In a previous study of our group cDNA of TMEM45A gene was detected as differentially expressed between healthy cervical tissue and a high grade squamous intraepithelial lesion (HSIL) with confirmed HPV-18 transforming infection. TMEM45A gene family is highly expressed in squamous epithelium, playing roles in differentiation, senescence and chemoresistance in some sort of epithelial carcinomas. The overexpression of this product may confer antiapoptotic pathways, contributing to the development of cervical squamous cell carcinoma. We compared the TMEM45A in situ mRNA expression in healthy cervical tissue, low grade squamous intraepithelial lesion (LSIL) and HSIL, using RNAscope chromogenic in situ hybridization (CISH). Design: TMEM45A expression was evaluated by CISH using a tissue microarray (TMA) constructed from cervical excision samples (conization and histerectomy) from 169 patients, with a mean age of 35.37 years (SD ±10.4), from a reference center for cervical pathology in the Colombian Caribbean. Stained sections from the donor blocks were reviewed by two pathologist, verifying the original sign-out diagnosis, and representative areas from normal cervix, LSIL and HSIL were selected. RNAscope 2.5HD Red TMEM45A assay was performed as a technical service in Advanced Cell Diagnostics´s laboratories (Newark, CA). The staining was visually scored by two pathologist from 0 to 4 based on the average number of dots per cell, according to a semi-quantitative analysis. The mean score values for each lesion group were compared using GraphPad Prism 7.0 software. A p&amp;lt; 0.05 was considered statistically significant. Results: The TMEM45A mRNA in situ expression was determined in a cervical TMA including, normal cervix: 76, LSIL: 69, and HSIL: 138, tissue cores. There was a higher mean staining score for TMEM45A mRNA in HSIL (1.51, 95% CI:1.26-1.76), compared to normal cervix (1.10, 95% CI:0.80-1.40). Mean score of TMEM45A in situ mRNA expression in HSIL was significantly higher than mean TMEM45A in situ mRNA expression in the normal cervix lining squamous epithelium (p=0.046). Conclusions: TMEM45A expression analysis identified differential expression between normal cervix lining squamous epithelium and HSIL. This finding supports the possible role of TMEM45A in carcinogenesis of well differentiated epithelial lesions. Additional studies to detect the TMEM45A expression at protein with samples of women from the Colombian Caribbean are in progress to validate these results. Citation Format: Ines Benedetti, Reinhard Rodríguez, Lia Barrios. Differences in mRNA expression of a candidate gene, between normal cervical tissue and cervical premalignant 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 2530.