Accuracy of combined protein gene product 9.5 and parafibromin markers for immunohistochemical diagnosis of parathyroid carcinoma.
BACKGROUND
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.


METHODS
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).


CONCLUSIONS
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.
Howell
Viive M
VM
Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia.
Gill
Anthony
A
Clarkson
Adele
A
Nelson
Anne E
AE
Dunne
Robert
R
Delbridge
Leigh W
LW
Robinson
Bruce G
BG
Teh
Bin T
BT
Gimm
Oliver
O
Marsh
Deborah J
DJ
D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008954:Models, Biological; D009154:Mutation / Q000502:physiology; D009367:Neoplasm Staging; D010282:Parathyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; C454900:CDC73 protein, human; D025521:Tumor Suppressor Proteins; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase