Parafibromin and APC as Screening Markers for Malignant Potential in Atypical Parathyroid Adenomas
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Parafibromin and APC as Screening Markers for Malignant Potential in Atypical Parathyroid Adenomas C. Christofer Juhlin & Inga-Lena Nilsson & Kenth Johansson & Felix Haglund & Andrea Villablanca & Anders Höög & Catharina Larsson
Published online: 15 May 2010 # Springer Science+Business Media, LLC 2010
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 C. C. Juhlin (*) : I.-L. Nilsson : F. Haglund : A. Villablanca : C. Larsson Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, CMM L8:01, 171 76 Stockholm, Sweden e-mail: [email protected] C. C. Juhlin : A. Höög Department of Oncology–Pathology, Karolinska Institutet, Karolinska University Hospital Solna, CMM L8:01, 171 76 Stockholm, Sweden K. Johansson Department of Surgery, Västervik Hospital, 593 81 Västervik, Sweden
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. Keywords Parafibromin . HRPT2 . APC . Immunohistochemistry . Atypical parathyroid adenoma . Parathyroid carcinoma
Introduction Parathyroid carcinoma is the malignant form of primary hyperparathyroidism and is frequently associated with mortal outcome due to uncontrolled hypercalcaemia [1]. The diagnosis is made upon histopathological examination in which an invasive growth pattern or metastasis must be demonstrated. The diagnosis parathyroid carcinoma thus requires either vascular or perineural invasion, invasive growth into adjacent tissues and/or metastases [2]. However, a tumour classification which requires extension into adjacent tissues for proper identification of a malignant phenotype is not always optimal, as the tumour may already be incurable at the time of diagnosis. Furthermore, parathyroid tumours that have acquired
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