Expression of Parafibromin in Distant Metastatic Parathyroid Tumors in Patients with Advanced Secondary Hyperparathyroidism Due to Chronic Kidney Disease

Background Recently, somatic inactivating mutations in HRPT2 have been reported in the majority of sporadic parathyroid carcinoma in primary hyperparathyroidism (HPT). Parafibromin is a tumor suppressor protein encoded by HRPT2 , and loss of nuclear expression of parafibromin was found in approximat...

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Bibliographic Details
Published in:World journal of surgery 2008-05, Vol.32 (5), p.815-821
Main Authors: Tominaga, Yoshihiro, Tsuzuki, Toyonori, Matsuoka, Susumu, Uno, Nobuaki, Sato, Tetsuhiko, Shimabukuro, Syuichi, Goto, Norihiko, Nagasaka, Takaharu, Uchida, Kazuharu
Format: Article
Language:English
Subjects:
Abdominal Surgery
Adult
Biological and medical sciences
Cardiac Surgery
Chronic Kidney Disease
Cinacalcet
Cohort Studies
Disease-Free Survival
Endocrinopathies
Female
General aspects
General Surgery
Humans
Hyperparathyroidism, Secondary - etiology
Hyperparathyroidism, Secondary - metabolism
Hyperparathyroidism, Secondary - surgery
Kidney Failure, Chronic - etiology
Kidney Failure, Chronic - metabolism
Kidney Failure, Chronic - therapy
Male
Medical sciences
Medicine
Medicine & Public Health
Middle Aged
Non tumoral diseases. Target tissue resistance. Benign neoplasms
Parathyroid Carcinoma
Parathyroid Gland
Parathyroid Neoplasms - genetics
Parathyroid Neoplasms - pathology
Parathyroid Neoplasms - surgery
Parathyroid Tissue
Parathyroidectomy
Parathyroids. Parafollicular cells. Cholecalciferol. Phosphocalcic homeostasis (diseases)
Renal Dialysis
Retrospective Studies
Surgery
Thoracic Neoplasms - metabolism
Thoracic Neoplasms - secondary
Thoracic Neoplasms - surgery
Thoracic Surgery
Treatment Outcome
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - metabolism
Vascular Surgery
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Summary:Background Recently, somatic inactivating mutations in HRPT2 have been reported in the majority of sporadic parathyroid carcinoma in primary hyperparathyroidism (HPT). Parafibromin is a tumor suppressor protein encoded by HRPT2 , and loss of nuclear expression of parafibromin was found in approximately 70% of the carcinoma. In secondary HPT due to chronic kidney disease (CKD), parathyroid carcinoma is very rare and whether HRPT2 plays a role in the carcinogenesis in these cases is not clear. We evaluated the expression of parafibromin in hemodialysis patients with distant metastatic parathyroid tumors. Methods Between June 1973 and December 2006, 2,142 patients underwent parathyroidectomy (PTx) for secondary HPT in our department. We encountered five (0.23%) patients with distant metastatic parathyroid tumors. We evaluated the immunohistochemistry for parafibromin in eight primary parathyroid glands removed from the neck at the initial operation and/or at reoperation and seven distant metastatic tumors resected at reoperation. Results In only one lung metastatic parathyroid tumor, negative staining for parafibromin was detected. In the other three lung, two regional node, and one chest wall metastatic parathyroid tumor, parafibromin was strongly stained in the nuclei of the parathyroid cells. Among eight primary glands, except for one with weakly positive staining, the expression of parafibromin was detected diffusely and strongly. Conclusion We conclude that the inactivating mutations and/or allelic loss of the HRPT2 gene may not play a major role in parathyroid carcinogenesis in secondary HPT due to CKD, but in these cases cancer development may be associated with a heterogeneous genetic disorder.
ISSN:0364-2313
1432-2323
DOI:10.1007/s00268-007-9458-8