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Previous Volume 330:757-761 March 17, 1994 Number 11 Next

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ABSTRACT

Background The origin and molecular pathogenesis of parathyroid carcinoma are unknown. This life-threatening cause of primary hyperparathyroidism cannot be reliably distinguished from its benign counterpart on the basis of histopathological features alone. Because the PRAD1, or cyclin D1, gene, a cell-cycle regulator, has been implicated in a subgroup of benign parathyroid tumors, we examined the possibility that another cell-cycle regulator with possible functional links to PRAD1, the retinoblastoma tumor-suppressor gene (RB), might be involved in the molecular pathogenesis of parathyroid carcinoma.

Methods Parathyroid carcinomas from 9 patients and adenomas from 21 were studied for evidence of tumor-specific loss of RB gene DNA (allelic loss) by analysis of four DNA polymorphisms and for evidence of altered expression of RB protein by immunohistochemical staining.

Results All of 11 specimens from 5 patients with parathyroid carcinoma and informative DNA patterns and 1 of 19 specimens from 19 patients with parathyroid adenoma and informative DNA patterns lacked an RB allele. Fourteen of 16 specimens (88 percent) from the nine patients with carcinoma had abnormal expression of RB protein (a complete or predominant absence of nuclear staining for the protein). None of the 19 adenomas, including the tumor with loss of an RB allele, had unequivocally abnormal staining for RB protein.

Conclusions Inactivation of the RB gene is common in parathyroid carcinoma and is likely to be an important contributor to its molecular pathogenesis. The presence of such inactivation may help to distinguish benign from malignant parathyroid disease and may have useful diagnostic, prognostic, and therapeutic implications.

Source Information

From the Laboratory of Endocrine Oncology, Department of Medicine and Massachusetts General Hospital Cancer Center (V.L.C., A.A.), and the Department of Pathology, Massachusetts General Hospital and Harvard Medical School (A.T., A.L.V.), Boston; the Center for Biotechnology, Baylor College of Medicine, The Woodlands, Tex. (H.-J.X., S.-X.H., W.F.B.); and the Section of Endocrinology, Denver Veterans Affairs Medical Center and the University of Colorado Health Sciences Center, Denver (M.E.W.).

Address reprint requests to Dr. Arnold at Jackson 1021, Massachusetts General Hospital, Boston, MA 02114.

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