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Endocrine Abstracts (2015) 37 GP30.06 | DOI: 10.1530/endoabs.37.GP.30.06

1Laboratory of Molecular Biology, IRCCS Policlinico San Donato, San Donato Milanese (MI), Italy; 2Division of Pathology, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; 3Istituto Nazionale Genetica Molecolare (INGM) Romeo ed Enrica Invernizzi, Milan, Italy; 4Medical Genetics, IRCCS Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy; 5Endocrinology Unit, IRCCS Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy; 6Endocrine Unit 2, Department of Clinical and Experimental Medicine, University of Pisa, University Hospital of Pisa, Pisa, Italy; 7Endocrine Surgery, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; 8General Medicine Unit, AO Alessandro Manzoni, Lecco, Italy; 9Endocrine Surgery, IRCCS Ospedale San Raffaele, Milan, Italy; 10Endocrinology and Diabetology Unit, Department of Biomedical Sciences for Health, IRCCS Policlinico San Donato, University of Milan, San Donato Milanese (MI), Italy.


Though there is no evidence of a constitutive nuclear accumulation of β-catenin, the Wnt/β-catenin pathway might be deregulated in parathyroid tumours. We investigated unphosphorylated active β-catenin distribution by western blot in 16 typical parathyroid adenomas (PAds): β-catenin accumulation in the nuclear protein fractions varied from the levels detected in Caco-2 cells with constitutively active Wnt signalling (three PAds) to the levels measured in HEK293 cells with intact Wnt signalling (six PAds) and positively correlated with AXIN2 mRNA levels (r=0.546, P=0.03). The Wnt/β-catenin pathway is intimately connected to the embryonic pluripotent core circuitry. Therefore, we treated PAds-derived cells (n=3) with 10–20 mM lithium chloride for 72 h: we detected nuclear accumulation of β-catenin and concomitant increases in mRNA levels of NANOG, decreases of SOX2, no changes of POU5F1/OCT4. In PAds nuclear β-catenin levels positively correlated with the NANOG mRNA levels and negatively with the SOX2 mRNA levels. Immunohistochemistry of tumour sections (11 PAds and eight carcinomas (PCas)) identified cells expressing at nuclear level the stem cell genes: NANOG-expressing cells were more abundant in parathyroid carcinomas (40.0±5.8%; range 30–70%) than in PAds (11.4±4.5%; range 1–40%; P=0.01), while OCT4 was similarly detected in 5–20% of cells in both PAds and PCas and 42% of PAds showed SOX2-expressing cells. SOX2-expressing cells were more abundant in PAds than in PCas (15.8±5.9% vs 7.0±3.6%; P=0.05). Patients harbouring the PAds with detectable SOX2 transcripts (n=22) had a more severe hyperparathyroidism at diagnosis: serum PTH and calcium levels were higher than that in patients with SOX2-undetectable PAds (n=14; PTH: 324.2±248.0 pg/ml vs 150.2±56.0 pg/ml; P=0.014; calcium: 11.9±1.2 mg/dl vs 11.2±0.7 mg/dl, P=0.06). Immunofluorescence detected few cells coexpressing SOX2 and NANOG or OCT4, while parathyroid tumour cells expressing PTH were negative for all the stem cell genes. In conclusion, we firstly showed that i) a subset of parathyroid tumour cells express the pluripotent stem cell genes and ii) β-catenin might be involved in the regulation of the stem-like phenotype acquisition by a subset of parathyroid tumour cells.

Disclosure: This work was supported by the IRCCS Policlinico San Donato Research Found.

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