title: Parafibromin and APC as screening markers for malignant potential in atypical parathyroid adenomas.
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.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, CMM L8:01, 171 76 Stockholm, Sweden. christofer.juhlin@ki.se
authors.forename: C Christofer
authors.initials: CC
authors.lastname: Juhlin
authors.forename: Inga-Lena
authors.initials: IL
authors.lastname: Nilsson
authors.forename: Kenth
authors.initials: K
authors.lastname: Johansson
authors.forename: Felix
authors.initials: F
authors.lastname: Haglund
authors.forename: Andrea
authors.initials: A
authors.lastname: Villablanca
authors.forename: Anders
authors.initials: A
authors.lastname: Höög
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000096:biosynthesis* / Q000235:genetics; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010282:Parathyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor; C454900:CDC73 protein, human; D025521:Tumor Suppressor Proteins
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