Loss of expression for the Wnt pathway components adenomatous polyposis coli and glycogen synthase kinase 3-β in parathyroid carcinomas

  • Authors:
    • C. Christofer Juhlin
    • Felix Haglund
    • Andrea Villablanca
    • Lars Forsberg
    • Kerstin Sandelin
    • Robert Bränström
    • Catharina Larsson
    • Anders Höög
  • View Affiliations

  • Published online on: February 1, 2009     https://doi.org/10.3892/ijo_00000173
  • Pages: 481-492
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Abstract

The development of parathyroid carcinoma has been associated with inactivating mutations of the Hyperparathyroidism type 2 (HRPT2) gene encoding parafibromin, a member of the human RNA Polymerase II-Associated Factor Complex (hPAF) and functionally linked to the Wingless type (Wnt) pathway. In this study, we characterized the expression of Wnt pathway molecules in parathyroid benign and malignant tumors. Tumors were investigated by immunohistochemistry supplemented with Western blot analyses using monoclonal antibodies. The study comprised 13 tumors from 12 cases of unequivocal parathyroid carcinoma, 18 cases of parathyroid adenoma, as well as non-tumorous parathyroid tissue. Adenomatous polyposis coli (APC) was uniformly expressed in non-tumorous parathyroid tissue and adenomas, but absent in carcinomas from 9 of 12 patients (75%). Expression of glycogen synthase kinase 3-β (GSK3-β) was lost in 4/12 carcinomas and in 1/18 adenomas. The loss of APC and GSK3-β did not lead to augmentation of the Wnt target protein cyclin D1 or the Wnt oncoprotein β-catenin. Active β-catenin showed cytoplasmic and nuclear expression in all non-tumorous tissues and tumors. Loss of APC immunoreactivity was significantly associated with parathyroid carcinoma as compared to adenomas (p<0.001), giving a high specificity (100%) and sensitivity (75%) for the detection of parathyroid malignancy. The results suggest the involvement of Wnt-pathway members APC and GSK3-β in parathyroid carcinoma development. In addition, APC immunohistochemistry could become a useful tool for improved recognition of parathyroid carcinoma together with immunohistochemistry for parafibromin and proliferation index. Furthermore, the involvement of APC related pathways in the disease development opens possibilities to explore therapeutic routes complementary to surgery.

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February 2009
Volume 34 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Juhlin, C.C., Haglund, F., Villablanca, A., Forsberg, L., Sandelin, K., Bränström, R. ... Höög, A. (2009). Loss of expression for the Wnt pathway components adenomatous polyposis coli and glycogen synthase kinase 3-β in parathyroid carcinomas. International Journal of Oncology, 34, 481-492. https://doi.org/10.3892/ijo_00000173
MLA
Juhlin, C. C., Haglund, F., Villablanca, A., Forsberg, L., Sandelin, K., Bränström, R., Larsson, C., Höög, A."Loss of expression for the Wnt pathway components adenomatous polyposis coli and glycogen synthase kinase 3-β in parathyroid carcinomas". International Journal of Oncology 34.2 (2009): 481-492.
Chicago
Juhlin, C. C., Haglund, F., Villablanca, A., Forsberg, L., Sandelin, K., Bränström, R., Larsson, C., Höög, A."Loss of expression for the Wnt pathway components adenomatous polyposis coli and glycogen synthase kinase 3-β in parathyroid carcinomas". International Journal of Oncology 34, no. 2 (2009): 481-492. https://doi.org/10.3892/ijo_00000173