MicroRNA expression associated with low-grade cervical intraepithelial neoplasia outcomes.

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.

Metastatic Papillary Thyroid Cancer to the Liver: The Central Role of a Multidisciplinary Approach to Treatment.

Background: Differentiated thyroid cancer (DTC) is comprised of papillary and follicular subtypes, and both have an overall excellent long-term prognosis. Patients with localized DTC that is successfully treated, usually with surgery, exhibit long-term survival well above 90%. In contrast, patients who develop distant metastatic disease have a significantly worse overall prognosis and outcome, often with disease that is refractory to conventional therapy such as surgery, radioactive iodine, and hormone suppression. For patients who recur with distant metastatic disease, limited effective treatment options are available, and most die of their disease within 5 years of recurrence. Case Report: We report the case of a 26-year-old female who presented with recurrent papillary thyroid cancer and a metastatic lesion isolated to the liver. Because of the extremely large size of the metastatic liver mass upon initial presentation, we took a neoadjuvant, multifaceted approach to treatment that included selective internal radioembolization therapy, an oral multikinase inhibitor, and surgical resection of the tumor mass after maximal reduction in tumor size. However, the patient died of metastatic DTC after 39 months of treatment. Conclusion: A multimodal, comprehensive approach to managing such complex patients is essential to optimize both the sequence and therapeutic approach to treatment.