Accuracy of Combined Protein Gene Product 9.5 and Parafibromin Markers for Immunohistochemical Diagnosis of Parathyroid Carcinoma

被引:96
作者
Howell, Viive M.
Gill, Anthony [2 ]
Clarkson, Adele [2 ]
Nelson, Anne E.
Dunne, Robert [4 ]
Delbridge, Leigh W. [3 ]
Robinson, Bruce G.
Teh, Bin T. [5 ]
Gimm, Oliver [6 ]
Marsh, Deborah J. [1 ]
机构
[1] Univ Sydney, Royal N Shore Hosp, Kolling Inst Med Res, Funct Genom Lab,Hormones & Canc Grp, St Leonards, NSW 2065, Australia
[2] Univ Sydney, Royal N Shore Hosp, Dept Anat Pathol, St Leonards, NSW 2065, Australia
[3] Univ Sydney, Royal N Shore Hosp, Endocrine Surg Unit, St Leonards, NSW 2065, Australia
[4] CSIRO, N Ryde, NSW 1670, Australia
[5] Van Andel Res Inst, Grand Rapids, MI 49503 USA
[6] Linkoping Univ Hosp, Dept Surg, SE-58185 Linkoping, Sweden
基金
英国医学研究理事会;
关键词
PROMOTER REGION; CELL CARCINOMA; BREAST-CANCER; HRPT2; GENE; EXPRESSION; PGP9.5; HYPERPARATHYROIDISM; MUTATIONS; ADENOMAS; TUMORS;
D O I
10.1210/jc.2008-1740
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: Parafibromin, encoded by HRPT2, is the first marker with significant benefit in the diagnosis of parathyroid carcinoma. However, because parafibromin is only involved in up to 70% of parathyroid carcinomas and loss of parafibromin immunoreactivity may not be observed in all cases of HRPT2 mutation, a complementary marker is needed. Objective: We sought to determine the efficacy of increased expression of protein gene product 9.5 (PGP9.5), encoded by ubiquitin carboxyl-terminal esterase L1 (UCHL1) as an additional marker to loss of parafibromin immunoreactivity for the diagnosis of parathyroid carcinoma. Design: In total, 146 parathyroid tumors and nine normal tissues were analyzed for the expression of parafibromin and PGP9.5 by immunohistochemistry and for UCHL1 by quantitative RT-PCR. These samples included six hyperparathyroidism-jaw tumor syndrome-related tumors and 24 sporadic carcinomas. Results: In tumors with evidence of malignancy, strong staining for PGP9.5 had a sensitivity of 78% for the detection of parathyroid carcinoma and/or HRPT2 mutation and a specificity of 100%. Complete lack of nuclear parafibromin staining had a sensitivity of 67% and a specificity of 100%. PGP9.5 was positive in a tumor with the HRPT2 mutation L64P that expressed parafibromin. Furthermore, UCHL1 was highly expressed in the carcinoma/hyperparathyroidism-jaw tumor syndrome group compared to normal (P < 0.05) and benign specimens (P < 0.001). Conclusion: These results suggest that positive staining for PGP9.5 has utility as a marker for parathyroid malignancy, with a slightly superior sensitivity (P = 0.03) and similar high specificity to that of parafibromin. (J Clin Endocrinol Metab 94: 434-441, 2009)
引用
收藏
页码:434 / 441
页数:8
相关论文
共 40 条
[1]  
[Anonymous], WHO CLASSIFICATION T
[2]   Altered gene expression in cells from patients with lysosomal storage disorders suggests impairment of the ubiquitin pathway [J].
Bifsha, P. ;
Landry, K. ;
Ashmarina, L. ;
Durand, S. ;
Seyrantepe, V. ;
Trudel, S. ;
Quiniou, C. ;
Chemtob, S. ;
Xu, Y. ;
Gravel, R. A. ;
Sladek, R. ;
Pshezhetsky, A. V. .
CELL DEATH AND DIFFERENTIATION, 2007, 14 (03) :511-523
[3]   Interaction and colocalization of PGP9.5 with JAB1 and p27Kip1 [J].
Caballero, OL ;
Resto, V ;
Patturajan, M ;
Meerzaman, D ;
Guo, MZ ;
Engles, J ;
Yochem, R ;
Ratovitski, E ;
Sidransky, D ;
Jen, J .
ONCOGENE, 2002, 21 (19) :3003-3010
[4]   HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome [J].
Carpten, JD ;
Robbins, CM ;
Villablanca, A ;
Forsberg, L ;
Presciuttini, S ;
Bailey-Wilson, J ;
Simonds, WF ;
Gillanders, EM ;
Kennedy, AM ;
Chen, JD ;
Agarwal, SK ;
Sood, R ;
Jones, MP ;
Moses, TY ;
Haven, C ;
Petillo, D ;
Leotlela, PD ;
Harding, B ;
Cameron, D ;
Pannett, AA ;
Höög, A ;
Heath, H ;
James-Newton, LA ;
Robinson, B ;
Zarbo, RJ ;
Cavaco, BM ;
Wassif, W ;
Perrier, ND ;
Rosen, IB ;
Kristoffersson, U ;
Turnpenny, PD ;
Farnebo, LO ;
Besser, GM ;
Jackson, CE ;
Morreau, H ;
Trent, JM ;
Thakker, RV ;
Marx, SJ ;
Teh, BT ;
Larsson, C ;
Hobbs, MR .
NATURE GENETICS, 2002, 32 (04) :676-680
[5]   Genetic analyses of the HRPT2 gene in primary hyperparathyroidism:: Germline and somatic mutations in familial and sporadic parathyroid tumors [J].
Cetani, F ;
Pardi, E ;
Borsari, S ;
Viacava, P ;
Dipollina, G ;
Cianferotti, L ;
Ambrogini, E ;
Gazzerro, E ;
Colussi, G ;
Berti, P ;
Miccoli, P ;
Pinchera, A ;
Marcocci, C .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2004, 89 (11) :5583-5591
[6]   Should parafibromin staining replace HRTP2 gene analysis as an additional tool for histologic diagnosis of parathyroid carcinoma? [J].
Cetani, Filomena ;
Ambrogini, Elena ;
Viacava, Paolo ;
Pardi, Elena ;
Fanelli, Giovanni ;
Naccarato, Antonio Giuseppe ;
Borsari, Simona ;
Lemmi, Monica ;
Berti, Piero ;
Miccoli, Paolo ;
Pinchera, Aldo ;
Marcocci, Claudio .
EUROPEAN JOURNAL OF ENDOCRINOLOGY, 2007, 156 (05) :547-554
[7]  
DeLellis RA., 2004, World Health Organization Classification of Tumors. Pathology and Genetics of Tumors of Endocrine Organizations, P124
[8]  
Gill AJ, 2006, AM J SURG PATHOL, V30, P1140
[9]   Gene expression of parathyroid tumors: Molecular subclassification and identification of the potential malignant phenotype [J].
Haven, CJ ;
Howell, VM ;
Eilers, PHC ;
Dunne, R ;
Takahashi, M ;
van Puijenbroek, M ;
Furge, K ;
Kievit, J ;
Tan, MH ;
Fleuren, GJ ;
Robinson, BG ;
Delbridge, LW ;
Philips, J ;
Nelson, AE ;
Krause, U ;
Dralle, H ;
Hoang-Vu, C ;
Gimm, O ;
Morreau, H ;
Marsh, DJ ;
Teh, BT .
CANCER RESEARCH, 2004, 64 (20) :7405-7411
[10]   PGP9.5 as a candidate tumor marker for non-small-cell lung cancer [J].
Hibi, K ;
Westra, WH ;
Borges, M ;
Goodman, S ;
Sidransky, D ;
Jen, J .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 155 (03) :711-715