title: Tumour nuclear oestrogen receptor beta 1 correlates inversely with parathyroid tumour weight.
abstract: Primary hyperparathyroidism (PHPT) is a common endocrinopathy, frequently caused by a parathyroid adenoma, rarely by a parathyroid carcinoma that lacks effective oncological treatment. As the majority of cases are present in postmenopausal women, oestrogen signalling has been implicated in the tumourigenesis. Oestrogen receptor beta 1 (ERB1) and ERB2 have been recently identified in parathyroid adenomas, the former inducing genes coupled to tumour apoptosis. We applied immunohistochemistry and slide digitalisation to quantify nuclear ERB1 and ERB2 in 172 parathyroid adenomas, atypical adenomas and carcinomas, and ten normal parathyroid glands. All the normal parathyroid glands expressed ERB1 and ERB2. The majority of tumours expressed ERB1 (70.6%) at varying intensities, and ERB2 (96.5%) at strong intensities. Parathyroid carcinomas expressed ERB1 in three out of six cases and ERB2 in five out of six cases. The intensity of tumour nuclear ERB1 staining significantly correlated inversely with tumour weight (P=0.011), and patients whose tumours were classified as ERB1-negative had significantly greater tumour weight as well as higher serum calcium (P=0.002) and parathyroid hormone levels (P=0.003). Additionally, tumour nuclear ERB1 was not expressed differentially with respect to sex or age of the patient. Levels of tumour nuclear ERB2 did not correlate with clinical characteristics. In conclusion, decreased ERB1 immunoreactivity is associated with increased tumour weight in parathyroid adenomas. Given the previously reported correlation with tumour-suppressive signalling, selective oestrogen receptor modulation (SERMs) may play a role in the treatment of parathyroid carcinomas. Future studies of SERMs and oestrogen treatment in PHPT should consider tumour weight as a potential factor in pharmacological responsiveness.
authors: Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine Felix.Haglund@ki.se.
authors: Felix
authors: F
authors: Haglund
authors: Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine.
authors: Gustaf
authors: G
authors: Rosin
authors: Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine.
authors: Inga-Lena
authors: IL
authors: Nilsson
authors: Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine.
authors: C Christofer
authors: CC
authors: Juhlin
authors: Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine.
authors: Ylva
authors: Y
authors: Pernow
authors: Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine.
authors: Sophie
authors: S
authors: Norenstedt
authors: Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine.
authors: Andrii
authors: A
authors: Dinets
authors: Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine.
authors: Catharina
authors: C
authors: Larsson
authors: Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine.
authors: Johan
authors: J
authors: Hartman
authors: Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine Department of Oncology-PathologyKarolinska Institutet, Stockholm, SwedenCancer Centre KarolinskaR8:04, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, SwedenDepartment of Biosciences and NutritionKarolinska Institutet, Novum, Huddinge, Stockholm, SwedenDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Stockholm, SwedenDepartment of Surgery #4Bogomolets National Medical University, Kiev, Ukraine.
authors: Anders
authors: A
authors: Höög
keywords: Visiopharm; oestrogen; oestrogen receptor beta; parathyroid adenoma; parathyroid carcinoma; primary hyperparathyroidism; selective oestrogen receptor modulators
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