TY - JOUR
T1 - CDC73 mutations and parafibromin immunohistochemistry in parathyroid tumors
T2 - Clinical correlations in a single-centre patient cohort
AU - Guarnieri, Vito
AU - Battista, Claudia
AU - Muscarella, Lucia Anna
AU - Bisceglia, Michele
AU - De Martino, Danilo
AU - Baorda, Filomena
AU - Maiello, Evaristo
AU - D'Agruma, Leonardo
AU - Chiodini, Iacopo
AU - Clemente, Celeste
AU - Minisola, Salvatore
AU - Romagnoli, Elisabetta
AU - Corbetta, Sabrina
AU - Viti, Raffaella
AU - Eller-Vainicher, Cristina
AU - Spada, Anna
AU - Iacobellis, Michela
AU - Malavolta, Nazzarena
AU - Carella, Massimo
AU - Canaff, Lucie
AU - Hendy, Geoffrey N.
AU - Cole, David E C
AU - Scillitani, Alfredo
PY - 2012
Y1 - 2012
N2 - Objective To determine if molecular and immunohistochemical (IHC) features of the HRPT2/CDC73 gene and its product, parafibromin, predict the natural history of parathyroid malignancy, particularly atypical adenoma, as seen in a single-centre patient cohort. Methods Matched tumor and non-tumor tissues were obtained from 46 patients with parathyroid carcinoma (CA) (n015), atypical adenoma (AA) (n014) and typical adenoma (TA) (n017), as defined by standardized histopathological criteria. Exons and exon-intron boundaries of the CDC73 gene were sequenced to identify germline or somatic mutations. IHC staining for parafibromin was performed and scored as positive if nuclear staining was at least partially IHC-positive. Results Mutations of CDC73 were observed in 9/15 (60 %) CA, 2/14 (14 %) AA, and 1/17 (6 %) TA tumors. A recurrent two basepair mutation in exon 7 - c.679-680delAG - accounted for half of all identified mutations. Absence of parafibromin nuclear staining was noted in 8/12 (67 %) CA, 2/13 (15 %) AA, and 3/17 (18 %) TA tumors. Median follow up times were 88 months for CA, 76 months for AA, and 104 months for TA patients. One patient, a member of a previously reported multiplex family with a germline CDC73 mutation was found to have a second adenoma after removal of an atypical adenoma. Conclusions Molecular screening and IHC are both useful tools in the differential diagnosis of parathyroid tumors, but both have limited sensitivity and specificity. CDC73 mutations and negative immunostaining were common in atypical adenomas, but no local recurrence was observed in any case with successful surgical removal after follow-up periods of 27 to 210 months.
AB - Objective To determine if molecular and immunohistochemical (IHC) features of the HRPT2/CDC73 gene and its product, parafibromin, predict the natural history of parathyroid malignancy, particularly atypical adenoma, as seen in a single-centre patient cohort. Methods Matched tumor and non-tumor tissues were obtained from 46 patients with parathyroid carcinoma (CA) (n015), atypical adenoma (AA) (n014) and typical adenoma (TA) (n017), as defined by standardized histopathological criteria. Exons and exon-intron boundaries of the CDC73 gene were sequenced to identify germline or somatic mutations. IHC staining for parafibromin was performed and scored as positive if nuclear staining was at least partially IHC-positive. Results Mutations of CDC73 were observed in 9/15 (60 %) CA, 2/14 (14 %) AA, and 1/17 (6 %) TA tumors. A recurrent two basepair mutation in exon 7 - c.679-680delAG - accounted for half of all identified mutations. Absence of parafibromin nuclear staining was noted in 8/12 (67 %) CA, 2/13 (15 %) AA, and 3/17 (18 %) TA tumors. Median follow up times were 88 months for CA, 76 months for AA, and 104 months for TA patients. One patient, a member of a previously reported multiplex family with a germline CDC73 mutation was found to have a second adenoma after removal of an atypical adenoma. Conclusions Molecular screening and IHC are both useful tools in the differential diagnosis of parathyroid tumors, but both have limited sensitivity and specificity. CDC73 mutations and negative immunostaining were common in atypical adenomas, but no local recurrence was observed in any case with successful surgical removal after follow-up periods of 27 to 210 months.
KW - Atypical adenoma
KW - CDC73
KW - HRPT2
KW - Parafibromin
KW - Parathyroid tumours
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U2 - 10.1007/s13402-012-0100-x
DO - 10.1007/s13402-012-0100-x
M3 - Article
C2 - 22987117
AN - SCOPUS:84878168394
VL - 35
SP - 411
EP - 422
JO - Cellular oncology (Dordrecht)
JF - Cellular oncology (Dordrecht)
SN - 2211-3428
IS - 6
ER -