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Nodal metastasis microRNA expression correlates with the primary tumour in MTC

Authors

  • Justin S. Gundara,

    1. Cancer Genetics Laboratory, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
    2. Endocrine Surgical Unit, Royal North Shore Hospital, Sydney, New South Wales, Australia
    3. University of Sydney, Sydney, New South Wales, Australia
    4. Northern Translational Cancer Research Unit, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
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  • Jing Ting Zhao,

    1. Cancer Genetics Laboratory, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
    2. University of Sydney, Sydney, New South Wales, Australia
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  • Anthony J. Gill,

    1. Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia
    2. University of Sydney, Sydney, New South Wales, Australia
    3. Northern Translational Cancer Research Unit, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
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  • Roderick Clifton-Bligh,

    1. Cancer Genetics Laboratory, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
    2. Department of Endocrinology, Royal North Shore Hospital, Sydney, New South Wales, Australia
    3. University of Sydney, Sydney, New South Wales, Australia
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  • Bruce G. Robinson,

    1. Cancer Genetics Laboratory, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
    2. Department of Endocrinology, Royal North Shore Hospital, Sydney, New South Wales, Australia
    3. University of Sydney, Sydney, New South Wales, Australia
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  • Leigh Delbridge,

    1. Endocrine Surgical Unit, Royal North Shore Hospital, Sydney, New South Wales, Australia
    2. University of Sydney, Sydney, New South Wales, Australia
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  • Stan B. Sidhu

    Corresponding author
    1. Cancer Genetics Laboratory, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
    2. Endocrine Surgical Unit, Royal North Shore Hospital, Sydney, New South Wales, Australia
    3. University of Sydney, Sydney, New South Wales, Australia
    • Correspondence

      Professor Stan B. Sidhu, Level 2, 69 Christie Street, St. Leonards, NSW 2065, Australia. Email: stansidhu@nebsc.com.au

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  • J. S. Gundara MBBS (Hons); J. T. Zhao PhD; A. J. Gill MD, FRCPA; R. Clifton-Bligh PhD, FRACP; B. G. Robinson MD, FRACP; L. Delbridge MD, FRACS; S. B. Sidhu PhD, FRACS.
  • Research Support: J. S. Gundara is supported by the Royal Australasian College of Surgeons Sir Roy McCaughey Surgical Research Fellowship.

Abstract

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.

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