Parafibromin, Galectin‐3, PGP9.5, Ki67, and Cyclin D1: Using an Immunohistochemical Panel to Aid in the Diagnosis of Parathyroid Cancer

Truran, Peter; Johnson, Sarah J.; Bliss, Richard; Lennard, T. W. J.; Aspinall, Sebastian

doi:10.1007/s00268-014-2700-2

Cited by 65 publications

(54 citation statements)

References 83 publications

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“…Recently, whole-genome sequencing uncovered additional mutations in parathyroid carcinomas, implicating PRUNE2 (∼18%), mTOR, MLL2, THRAP3 and PIK3CA genes 141 226 227. Overexpression of PGP9.5 (gene product of UCHL1 gene), galectin-3 and TERT (telomerase reverse transcriptase gene) were also described in some parathyroid carcinomas 160 223 230. Previous comparative genomic hybridisation and molecular allelotyping studies on parathyroid carcinomas also revealed losses on chromosomes 1p, 3, 13q and 14 and gains on chromosomes 1q and 16 42 141.…”

Section: Pathogenesis and Molecular Genetics Of Hptmentioning

confidence: 99%

Clinicopathological correlates of hyperparathyroidism

2015

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Hyperparathyroidism is a common endocrine disorder with potential complications on the skeletal, renal, neurocognitive and cardiovascular systems. While most cases (95%) occur sporadically, about 5% are associated with a hereditary syndrome: multiple endocrine neoplasia syndromes (MEN-1, MEN-2A, MEN-4), hyperparathyroidism-jaw tumour syndrome (HPT-JT), familial hypocalciuric hypercalcaemia (FHH-1, FHH-2, FHH-3), familial hypercalciuric hypercalcaemia, neonatal severe hyperparathyroidism and isolated familial hyperparathyroidism. Recently, molecular mechanisms underlying possible tumour suppressor genes (MEN1, CDC73/HRPT2, CDKIs, APC, SFRPs, GSK3β, RASSF1A, HIC1, RIZ1, WT1, CaSR, GNA11, AP2S1) and proto-oncogenes (CCND1/PRAD1, RET, ZFX, CTNNB1, EZH2) have been uncovered in the pathogenesis of hyperparathyroidism. While bi-allelic inactivation of CDC73/HRPT2 seems unique to parathyroid malignancy, aberrant activation of cyclin D1 and Wnt/β-catenin signalling has been reported in benign and malignant parathyroid tumours. Clinicopathological correlates of primary hyperparathyroidism include parathyroid adenoma (80–85%), hyperplasia (10–15%) and carcinoma (<1–5%). Secondary hyperparathyroidism generally presents with diffuse parathyroid hyperplasia, whereas tertiary hyperparathyroidism reflects the emergence of autonomous parathyroid hormone (PTH)-producing neoplasm(s) from secondary parathyroid hyperplasia. Surgical resection of abnormal parathyroid tissue remains the only curative treatment in primary hyperparathyroidism, and parathyroidectomy specimens are frequently encountered in this setting. Clinical and biochemical features, including intraoperative PTH levels, number, weight and size of the affected parathyroid gland(s), are crucial parameters to consider when rendering an accurate diagnosis of parathyroid proliferations. This review provides an update on the expanding knowledge of hyperparathyroidism and highlights the clinicopathological correlations of this prevalent disease.

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Section: Pathogenesis and Molecular Genetics Of Hptmentioning

confidence: 99%

Clinicopathological correlates of hyperparathyroidism

2015

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“…Even though the AUROC for parafibromin staining was 0.91 and the pooled specificity was 95 %, the pooled sensitivity was limited (68 %). Combined IHC analysis with other biomarkers such as galectin-3, Ki-67, p27, and protein gene product 9.5 (PGP95) was believed to be better than any single marker in diagnosing PTCA [27]. A significant heterogeneity was noted in sensitivity and specificity across included studies.…”

Section: Discussionmentioning

confidence: 97%

“…1. From 286 potentially relevant publications, a total of 10 studies were eligible for data extraction and analysis [15][16][17][23][24][25][26][27][28][29]. The characteristics of these included …”

Section: Eligible Articlesmentioning

confidence: 99%

Diagnostic performance of parafibromin immunohistochemical staining for sporadic parathyroid carcinoma: a meta-analysis

Liao

Cao

et al. 2016

Endocrine

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It is a challenge to distinguish parathyroid carcinoma (PTCA) from benign parathyroid lesions without recurrence or metastasis. Parafibromin immunohistochemical (IHC) staining had been described for the diagnosis of PTCA. But great variations existed in the reported sensitivity and specificity among different studies. We conducted a meta-analysis to summarize the diagnostic accuracy of parafibromin staining for PTCA. Published studies from Pubmed, Embase, and Cochrane Library were searched using the combination of terms "parafibromin," "CDC73," "HRPT2," and "parathyroid." Pooled sensitivity and specificity with 95 % confidence interval (CI) were calculated and the summary receiver operator characteristic (SROC) curves were constructed. The heterogeneity among included studies was evaluated and possible reasons were explored by meta-regression. A total of 10 studies including 202 patients with PTCA were finally enrolled in this meta-analysis. For parafibromin staining, sensitivity varied from 29 to 100 % (pooled estimate of 68 %; 95 % CI 49-82 %) and specificity ranged from 61 to 100 % (pooled estimate of 95 %; 95 % CI 85-98 %). The AUC for parafibromin staining was 0.91 (95 % CI 0.88-0.93). A significant heterogeneity was observed among included studies. According to meta-regression analysis, the scoring criteria and parafibromin antibody used in IHC were the covariates influencing the sensitivity. And the specificity decreased if atypical parathyroid adenomas were included in the control groups. The specificity of parafibromin staining was satisfactory for diagnosis of PTCA, while the sensitivity was limited. We suggested that a standardized IHC protocol and scoring system criteria should be applied in future studies to improve the diagnostic performance of parafibromin staining.

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“…Hence, it has been advocated that increased expression of PGP9.5 protein with loss of parafibromin nuclear staining should be used to screen for CDC73 mutation and PC [67,68]. Despite these restraints, the immunohistochemical panel that is usually used contains parafibromin, galactin-3, PGP9.5, and Ki-67 [70].…”

Section: Pathologic Diagnosismentioning

confidence: 99%

Current Understanding and Management of Parathyroid Carcinoma

Arrangoiz¹

2017

JCTR

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Parathyroid adenomas are a very common endocrine entity, whereas parathyroid carcinomas (PC) are extremely rare. With an estimated incidence of 0.015 per 100,000 population and an estimated prevalence of 0.005% in the United States, parathyroid cancer is one of the rarest of all human malignancies. PC is an extremely rare cause of primary hyperparathyroidism (PHPT). Men and women are equally affected, usually in the fourth or fifth decade of life. The exact etiology has not been identified, but mutations in the CDC73 gene appear to have a critical role in its pathogenesis. The morbidity and mortality of PC is secondary to the hypercalcemia resulting from tumor overproduction of PTH. The primary management objectives are complete removal of the cancer and prevention of recurrences. This review will talk about the epidemiology, etiology, clinical manifestations, and management of PC.

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Parafibromin, Galectin‐3, PGP9.5, Ki67, and Cyclin D1: Using an Immunohistochemical Panel to Aid in the Diagnosis of Parathyroid Cancer

Abstract: A panel of immunohistochemistry (PGP9.5, galectin-3, parafibromin, and Ki67) is better than any single marker and can be used to supplement classical histopathology in diagnosing parathyroid cancer.

Cited by 65 publications

References 83 publications

Clinicopathological correlates of hyperparathyroidism

Clinicopathological correlates of hyperparathyroidism

Diagnostic performance of parafibromin immunohistochemical staining for sporadic parathyroid carcinoma: a meta-analysis

Current Understanding and Management of Parathyroid Carcinoma

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