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Negative/Low Expression of the Met/Hepatocyte Growth Factor Receptor Identifies Papillary Thyroid Carcinomas with High Risk of Distant Metastases¹

Istituto di Medicina Interna e di Malattie Endocrine e del Metabolismo, Cattedra di Endocrinologia, University of Catania; Servizio di Anatomia Patologica, Ospedale V. Emanuele II (P.G., G.R., A.F.); and Cattedra di Chirurgia, University of Catania (O.I.), Catania; and Dipartimento di Scienze Biomediche ed Oncologia, University of Torino (M.F.D.R., P.C.), Torino, Italy

Address all correspondence and requests for reprints to: Antonino Belfiore, M.D., Istituto di Medicina Interna e di Malattie Endocrine e del Metabolismo, Cattedra di Endocrinologia, Ospedale Garibaldi, Piazza S. Maria di Gesù 1, 95123 Catania, Italy. E-mail: segmeint{at}mbox.unict.it

To investigate the clinical impact of Met/hepatocyte growth factor receptor (HGF-R) expression in thyroid cancer we studied 163 thyroid carcinomas (129 papillary, 21 follicular, and 13 anaplastic) from patients followed-up for 25–147 months postthyroidectomy. Forty-nine thyroid adenomas were also studied. Met/HGF-R expression was evaluated by semiquantitative immunohistochemistry, measuring both the proportion (scale of 0–5) and the intensity (scale, 0–5) of stained cells and calculating a total score (scale of 0–10).

Met/HGF-R was absent in the normal thyroid tissue, absent or focally expressed in follicular and anaplastic tumors, and expressed at various levels in most papillary carcinomas, including microcarcinomas. Papillary carcinomas were thus categorized as having negative/low Met/HGF-R (n = 50; total score, 5) or high Met/HGF-R expression (n = 70; total score, >5). High Met/HGF-R was inversely associated with vascular invasion (P = 0.0308), but not with other prognostic factors. Negative/low Met/HGF-R expression was the most effective predictor by multivariate Cox analysis of distant metastases (hazard ratio = 9.71; P = 0.0036), higher than extrathyroid invasion (hazard ratio = 4.25; P = 0.0181), age (45 vs. >45 yr; hazard ratio = 3.99; P = 0.0099), and vascular invasion (hazard ratio = 3.19; P = 0.0358). These findings suggest a role for Met/HGF-R in papillary thyroid cancer and its clinical use to select patients with a high risk of distant metastases.

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