Unique expression pattern of the EMT markers Snail, Twist and E-cadherin in benign and malignant parathyroid neoplasia
Volker FendrichJens WaldmannGeorg FeldmannKatja SchlosserAlexander KönigAnnette RamaswamyDetlef K. BartschElias Karakas
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Abstract:
Background Epithelial and mesenchymal transitions (EMT) are essential for embryonic development and progression of non-invasive tumor cells into malignant, metastatic carcinomas. During embryogenesis, the parathyroid glands develop from pharyngeal pouches and migrate to their final destinations, densely enclosed by mesenchymal neural crest cells. In this study, we examined the expression of the EMT markers Snail, Twist and E-cadherin in normal parathyroid glands and benign and malignant parathyroid diseases. Methods Using immunohistochemistry, we compared expression of E-cadherin, Snail and Twist in 25 patients with parathyroid adenoma, 25 patients with parathyroid hyperplasia, and nine patients with parathyroid cancer with normal parathyroid glands. Results Normal parathyroid glands, parathyroid adenomas, and parathyroid hyperplasias showed a typical membranous E-cadherin staining pattern. Expression of Snail was found in 22/25 parathyroid adenomas and in all parathyroid hyperplasias. Twist was expressed in 22/25 of parathyroid adenomas and in 20/25 parathyroid hyperplasias. Snail and Twist positive cells were homogeneously distributed throughout the gland. However, in all nine parathyroid carcinomas, membranous E-cadherin staining was lost. In addition, the expression pattern of Snail and Twist was changed and mostly limited to the invasive front of cancer tissue samples. Conclusion Expression of Snail and Twist at the invasive front and consecutive loss of E-cadherin in parathyroid carcinomas suggests a key role of EMT in the tumorigenesis of this cancer. The unique expression pattern could help to distinguish between an adenoma and a non-metastatic carcinoma. Loss of E-cadherin and change of the expression pattern of Snail and Twist together should result in an en bloc resection or a close follow-up.Keywords:
Parathyroid carcinoma
Parathyroid neoplasm
Parathyroid chief cell
Objective:To investigate the expression of cyclin D1 in parathyroid tissues and its clinical significance. Methods:Immunohistochemical method was used to detect the expression of cyclin D1 in 3 parathyroid carcinoma tissues,8 parathyroid adenoma tissues,and 13 proliferative parathyroid tissues,1 parathyroid cyst,and 10 normal parathyroid tissues. Results:The overexpression ratio of cyclin D1 was significantly higher in parathyroid adenoma group and parathyroid carcinoma group than that in normal parathyroid group (P0.05). There was no significant difference between parathyroid proliferation group and parathyroid carcinoma group,or parathyroid adenoma group,or normal parathyroid group (P0.05). Conclusion:The overexpression of cyclin D1 played an important role in parathyroid adenoma and parathyroid carcinoma. Cyclin D1 might contribute to the etiology of parathyroid adenoma and carcinoma.
Parathyroid carcinoma
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Parathyroid carcinoma
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Surgical oncology
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Parathyroid carcinoma
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Parathyroid carcinoma, atypical parathyroid adenoma, and parathyromatosis can be differentiated relatively easily from typical parathyroid adenomas, but distinguishing them from each other is more difficult.A retrospective study of 28 consecutive patients with parathyroid carcinoma, 7 patients with atypical parathyroid adenoma, and 13 patients with parathyromatosis who were treated at the University of California at San Francisco Medical Center between 1966 and 2005 was performed. Patient demographics and clinical characteristics, indication for surgery, intraoperative findings, histopathologic characteristics, disease recurrence or persistence, site of invasion/metastases, and survival were compared in the 3 groups.Parathyroid carcinoma (19 of 28 patients) and atypical adenoma (4 of 7 patients) were significantly more common in men, whereas parathyromatosis was more common in women (10 of 13 patients) (P = .02). A palpable neck mass and hoarseness were almost exclusively present in patients with parathyroid carcinoma. Prior to the first parathyroid surgery, patients with parathyroid carcinoma were found to have higher blood calcium levels (>/=14 mg/dL in 16 of 26 patients [62%]), whereas only 1 of 6 patients with atypical adenoma (17%) and no patients with parathyromatosis were found to have profound hypercalcemia (P < .01). Intraoperatively, patients with parathyroid carcinoma and atypical adenoma presented with single lesions, whereas patients with parathyromatosis had multiple small lesions. Histopathologic findings were well defined in parathyroid carcinoma, but some findings overlapped in the 3 tumors studied.Patients with parathyroid carcinoma often differ from those with atypical parathyroid adenoma or parathyromatosis at the time of presentation because patients with parathyroid carcinoma have more profound hypercalcemia as well as invasive tumors. However, at times it is difficult to distinguish between these conditions both clinically and by final histologic examination.
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Parathyroid carcinoma is one of the rare endocrine tumors and constitutes 1% of the cases with primary hyperparathyroidism. Because of similar imaging modalities and similar clinical findings, it is difficult to distinguish between preoperative parathyroid adenomas and parathyroid carcinoma. A 70-year-old female patient presented with fatigue and generalized bone pain. Her laboratory tests, neck and parathyroid scintigraphy were compatible with primary hyperparathyroidism with a significantly elevated level of parathormone. With the imaging methods which supported parathyroid adenoma, the patient was operated with a presumptive diagnosis of primary hyperparathyroidism due to parathyroid adenoma. The postoperative course was unremarkable and she was discharged on the postoperative fifth day. Postoperative pathology was reported as parathyroid carcinoma developed in a parathyroid adenoma. Parathyroid carcinoma and parathyroid adenoma have similar clinically and imaging methods, it is difficult to diagnose preoperatively.
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Tc-99m sestamibi (MIBI) is increasingly used for the preoperative localization of parathyroid adenoma. As experience is gained with this radiopharmaceutical, instances of uptake by non-adenomas will be encountered. A case of focal Tc-99m MIBI uptake by parathyroid carcinoma mimicking parathyroid adenoma is presented.
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To study the expression and clinical significance of CD147 in the patients of parathyroid carcinoma.Fourteen cases of parathyroid carcinoma encountered during the period from 2012 to 2015 were enrolled. Thirty three cases of parathyroid adenoma encountered during the same period were enrolled. The expression of CD147 in parathyroid carcinoma and parathyroid adenoma was studied by means of immunohistochemistry (EnVision method).CD147 positive color was brown and yellow, and positive position was located mainly in the cytomembrane, and a small amount of cytoplasm was appeared. Among 14 cases of parathyroid carcinoma, 11 cases of CD147 positive score was 3+ , 3 cases of CD147 positive score was 2+ ; Among 33 cases of parathyroid adenoma , 8 cases of CD147 positive score was 2+ , 15 cases of it was 1+ , 10 cases of it was negative. CD147 was highly expressed in parathyroid carcinoma tissues, and the expression of CD147 was significantly different from the expression of parathyroid adenoma(P<0.05).CD147 immunohistochemical staining can help to diagnose parathyroid carcinoma.
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As histopathological findings of parathyroid carcinoma are not certain, the diagnosis of tumors with degenerative changes may be difficult. In these cases, immunohistochemical markers are beneficial. We aimed to research the acceptability of calcium-sensing receptor (CaSR), Galactin-3, Cyclin D1, and Ki-67 as helpful markers in parathyroid tumors in cases which are difficult to diagnose.Those cases who had been diagnosed with atypical parathyroid adenoma and parathyroid carcinoma between 2010 and 2015 were reevaluated. İmmunohistochemical markers were applied to this cases.About 21 cases were parathyroid adenoma, 14 were atypical adenoma, and 10 cases were parathyroid carcinoma. According to the immunohistochemical results, global loss of CaSR staining was seen in 50% (5/10) of the patients with carcinoma while there was no loss of staining in those with parathyroid adenoma (P = 0,001). Global loss of CaSR staining was found in only one out of 14 cases with atypical adenoma. The expression of Galactin-3 was found to be positive in 40% (4/10) of carcinoma cases, 71.4% (10/14) of those with atypical adenoma, and 14.3% (3/21) of those with adenoma (P = 0,002). Cyclin D1 expression was determined to be positive in 70% (7/10) of patients with carcinoma, 71.4% (10/14) of atypical adenoma cases, and 23.8% (5/21) of those with adenoma. The Ki-67 proliferation index was seen to be above 5% in 50% (5/10) of carcinoma cases and 35,7% (5/14) of those with atypical adenoma.In these studies, it has been emphasized that the global loss of CaSR staining was used as a negative marker in the diagnosis of carcinoma. In this study, we have also confirmed that the global loss of CaSR staining is a useful marker to determine potential increased malignancy.
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