ABSTRACT
PURPOSE: Only a fraction of low-grade cervical intraepithelial neoplasia (CIN) progresses to high-grade CIN; however, the biological processes that differentiate progressive CIN from CIN that resolves naturally are poorly understood. MicroRNAs (miRNAs) are important epigenetic regulators of gene expression and thus, miRNA expression profiling can reveal the dysregulated biology underlying disease processes. The purpose of this case-control study was to reveal miRNA expression patterns and predict the underlying biological pathways that are associated with clinical outcomes of low-grade CIN. METHODS: Women with low-grade CIN diagnosis and definitive clinical outcomes (n = 51) were identified retrospectively using electronic clinical records. Comprehensive miRNA expression profiling was performed on the low-grade CIN diagnostic cervical biopsies retrieved from pathology archives. Differential miRNA expression was analyzed by comparing women with CIN that progressed to women with CIN that resolved naturally. RESULTS: Differential expression of 29 miRNAs was observed in low-grade CIN that progressed to high-grade compared to low-grade CIN that resolved. Of these, 24 were significantly downregulated in progressive CIN, including miR-638, miR-3196, miR-4488, and miR-4508, while 5 miRNAs, including miR-1206a, were significantly upregulated. Computational gene ontology analysis based on the discovered miRNAs and their putative mRNA targets revealed biological processes associated with oncogenic phenotypes. CONCLUSION: Distinct miRNA expression profiles are associated with clinical outcomes of low-grade CIN. The functional effects of the differentially expressed miRNAs may be biological determinants of CIN progression or resolution.
Subject(s)
MicroRNAs , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Case-Control Studies , Retrospective Studies , Gene Expression Regulation, Neoplastic , Uterine Cervical Dysplasia/pathology , MicroRNAs/genetics , MicroRNAs/metabolismABSTRACT
BACKGROUND: Squamous papillomas are exophytic proliferations of surface oral epithelium. Human papillomavirus (HPV) infection is widely accepted as the etiology of squamous papillomas however the virus cannot be detected in a significant percentage of lesions. MATERIAL AND METHODS: Using polymerase chain reaction (PCR), we tested 35 formalin-fixed paraffin-embedded (FFPE) squamous papillomas for the presence of HPV DNA. RESULTS: Six papillomas (17%) tested positive for HPV DNA; four contained HPV-6 and two contained HPV-11. Given that ß-globin DNA was only identified in half of the samples, DNA degradation appears to have significantly impacted the results. CONCLUSIONS: The results likely represent an underestimation of the true number of HPV-positive specimens in our study. Potential explanations for HPV-negative squamous papillomas include transient HPV infection, failure of the experiment to detect HPV if present, or the possibility that some lesions may not result from HPV infection. Key words:HPV, PCR, FFPE, papilloma, oral.
