CDNA array analysis of cytobrush-collected normal and malignant cervical epithelial cells: a feasibility study

Abstract

Analysis of gene expression pattern is a useful approach to evaluating the biological behavior and clinical outcome of several human malignancies. Differentially expressed genes in malignant squamous cervical cells and the feasibility of gene expression profiling on squamous cervical cells obtained from cervical swabs were investigated. Cervical squamous cells from three women with high-risk human papilloma virus (HR-HPV) positive invasive squamous cervical carcinoma and from three HPV-negative women with normal ectocervical smears were analyzed with cDNA array. Immunoblot analysis was performed to detect the proteins corresponding to the highest upregulated genes with cDNA array. mRNA expression of ERBB2, KIT, FLT1, MYCN, RAS, CDKN2A, CCND1, NME1, NME2, MET, FGF7, FGFR2, and STAT1 was increased in malignant samples. Several expressed genes associated with antiapoptosis (such as BCL2), cell structuring, or cell attachment were also upregulated in carcinoma cells. Decreased gene expression was observed for members of the transforming growth factor receptor superfamily (TGF) and integrin family, interleukin 1 ( IL1), and insulin-like growth factor binding proteins (IGFBPs). This study shows the feasibility of gene expression profiling of cervical squamous cells obtained with cytobrushes by identifying a characteristic gene expression pattern that clearly distinguishes between malignant and normal cervical epithelia of squamous type. We hypothesize that this noninvasive technique could be used in the evaluation of ambiguous Papanicolaou (PAP) smears.