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Parafibromin and APC as Screening Markers for Malignant Potential in Atypical Parathyroid Adenomas

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Abstract

The identification of parathyroid carcinomas is based upon histopathological criteria in which an invasive growth pattern or distant metastasis is demonstrated. A dilemma arises when tumours present with atypical histopathological features but lack direct evidence of malignancy. Recently, reduced expression or loss of the tumour suppressor proteins parafibromin and adenomatous polyposis coli (APC) has been associated with parathyroid malignancy. We report results from APC and parafibromin expression analyses by immunohistochemistry and Western blot in five cases of atypical adenoma, a single case of carcinoma and 54 adenomas without atypical features. Complete loss of APC immunoreactivity and reduced expression of parafibromin was evident in two of the atypical adenomas and in the parathyroid carcinoma. By contrast, all adenomas displayed APC expression, including two cases with hyperparathyroidism 2 gene (HRPT2) mutations and loss of parafibromin expression. We conclude that loss of APC is a frequent molecular event in atypical adenomas and carcinomas, but not in adenomas. Following verification in an independent material, APC could become a valuable tool when assessing parathyroid tumours in the clinical setting. Furthermore, the molecular resemblance of atypical adenomas with carcinoma concerning parafibromin and APC expression indicates that atypical adenomas should be subjects to watchful follow-up.

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Acknowledgements

The authors wish to thank Ms Elisabeth Ånfalk for valuable assistance in tumour collection. The study was financially supported by the Swedish Cancer Society, the Swedish Research Council, the Cancer Society in Stockholm, the Gustav V Jubilee Foundation, the Göran Gustafsson Foundation for Research on Natural Sciences and Medicine, the Stockholm County Council and Karolinska Institutet. The authors affirm that there is no conflict of interest that would prejudice the impartiality of this scientific work.

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Correspondence to C. Christofer Juhlin.

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Juhlin, C.C., Nilsson, IL., Johansson, K. et al. Parafibromin and APC as Screening Markers for Malignant Potential in Atypical Parathyroid Adenomas. Endocr Pathol 21, 166–177 (2010). https://doi.org/10.1007/s12022-010-9121-z

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