Nodal Metastasis MicroRNA Expression Correlates with the Primary Tumour in MTC

Introduction: Lymph node metastases represent a diagnostic and management challenge in patients with disseminated medullary thyroid carcinoma (MTC). Our understanding of microRNA (miRNA) profiles of metastatic disease also remains limited and may unveil novel therapeutic strategies for these patients.

Methods: MTC patients with a history of total thyroidectomy and lymph node dissection were identified from within the prospective Sydney University Endocrine Surgical Unit database. Patients with available formalin-fixed paraffin-embedded tumour tissue were included and clinicopathological data were collated. Total RNA was extracted and quantitave polymerase chain reaction (qPCR) analysis performed on the primary tumour and a corresponding lymph node metastasis for expression of miRNAs of proven significance in MTC (miR-9*, miR-183 and miR-375).

Results: Tissue was available for analysis in seven patients. The median age at diagnosis was 55 years (range: 22-67). Median tumour size was 18 mm (range: 6-55) and over a median follow-up period of 34 months (range: 1-210), five further operations were undertaken for residual disease. One patient died of metastatic disease. Pairwise correlations of qPCR expression levels between primary tumours and corresponding lymph node metastases revealed significant correlations for miR-9* (P < 0.001), miR-183 (P = 0.001) and miR-375 (P = 0.004).

Conclusion: miRNA expression patterns in nodal metastases significantly reflect those of the primary tumour in MTC. This further validates previously reported miRNA profile analyses and reiterates the potential significance of miR-9*, -183 and -375 in the pathophysiology of MTC. The possibility of lymph node biopsy miRNA analysis driven clinical decision making may now also be a possibility where conventional techniques are unhelpful.