OP106 – The precursor for nerve growth factor (proNGF) is detectable in the rinse of fine needle aspiration biopsies from thyroid cancers

      Rowe, Christopher1,2,3; Faulkner, Sam4; Tolosa, Jorge M.2,3; Paul Jonathan2,3; Gedye, Craig34,5; Smith, Roger1,2,3; Hondermarck, Hubert3,4 1 Department of Endocrinology, John Hunter Hospital, Newcastle, Australia 2 School of Medicine and Public Health, University of Newcastle, Newcastle, Australia 3 Hunter Medical Research Institute, Newcastle, Australia 4 School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia 5 Department of Medical Oncology, Calvary Mater Hospital, Newcastle, Australia   Background/ Purpose: Assessment of malignancy risk in thyroid nodules is problematic, particularly for follicular lesions which often require diagnostic hemithyroidectomy.  The precursor of nerve growth factor (proNGF) has been shown to be overexpressed in thyroid cancers using immunohistochemistry.1  We hypothesised that proNGF could be detected in the needle rinse of thyroidal fine needle aspiration biopsy and would discriminate between benign and malignant thyroid lesions. Methods: Consecutive, consenting patients of a thyroid biopsy clinic requiring diagnostic thyroid biopsy2 were enrolled.  A single 25-gauge needle pass under ultrasound guidance was rinsed in 0.5mL of phosphate-buffered saline with protease inhibitors, after the expulsion of cellular material.  ProNGF was detected using a human proNGF ELISA Kit, with limit of detection 0.078ng/mL.  Group assignment (benign, malignant) was based on surgical diagnosis (n=17), or concurring clinical/ultrasound/cytology assessment (n=32). Results: 49 patients were included, with mean age 54 +/- 16 years and 85% female.  ProNGF was detected in 4/11 biopsies from thyroid cancers (range 0.16-1.79ng/mL), compared to 4/38 biopsies from benign nodules (range 0.09-0.18ng/mL) (p=0.05, Mann-Whitney).  By histological subtype, 3/4 FTC, 1/6 PTC and 0/1 ATC were positive for proNGF.  The coefficient of variation for the assay was 2.3%.  Discussion: This pilot study shows for the first time that proNGF is detectable in the needle rinse of thyroid biopsy material.  Further, proNGF levels are significantly higher in biopsies from cancers, particularly FTC.  Larger studies are required to confirm these findings, and to determine whether proNGF may assist with risk stratification of follicular lesions.   References:
    1. Faulkner, S., Roselli, S., Demont, Y., Pundavela, J., Choquet, G., Leissner, P., Oldmeadow, C., Attia, J., Walker, M.M. & Hondermarck, H. (2016) ProNGF is a potential diagnostic biomarker for thyroid cancer. Oncotarget 7, 28488-28497.
    2. Haugen, B.R., Alexander, E.K., Bible, K.C., Doherty, G.M., Mandel, S.J., Nikiforov, Y.E., Pacini, F., Randolph, G.W., Sawka, A.M., Schlumberger, M., Schuff, K.G., Sherman, S.I., Sosa, J.A., Steward, D.L., Tuttle, R.M. & Wartofsky, L. (2016) 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 26, 1-133


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