Association of decreased calcium-sensing receptor expression with proliferation of parathyroid cells in secondary hyperparathyroidism

Yano, Shozo; Sugimoto, Toshitsugu; Tsukamoto, Tatsuo; Chihara, Kazuo; Kobayashi, Akira; Kitazawa, Sohei; Maeda, Shingo; Kitazawa, Riko

doi:10.1046/j.1523-1755.2000.00370.x

Cited by 43 publications

(60 citation statements)

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“…1f). These staining patterns were mostly uniform in PT adenomas, while hyperplastic PTGs from 28HPT showed heterogeneous staining intensity of each nodule in the glands, as we described previously (7). In semiquantitative analyses, the expression levels of both CaSR and VDR were significantly lower in the adenomas than in normal PTGs (Fig.…”

Section: Vdr and Casr Expression In Pt Adenomassupporting

confidence: 79%

“…Immunohistochemical staining was performed as previously described (7). Briefly, after deparaffinization and rehydration, sections were incubated with 0.3% H 2 O 2 in methanol for 20 min at room temperature to inactivate the endogenous peroxidase.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Semiquantitative analysis of immunohistochemical signals was performed using a modified version of the method described previously (7). In brief, areas for analyses were regularly selected on the H-E stain from every eight areas in each section, according to systematic random sampling (23).…”

Section: Quantification Of Immunohistochemical Signalsmentioning

confidence: 99%

“…Vitamin D suppresses not only PTH synthesis at the mRNA level but also PT cell proliferation (13,14). In addition, VDR expression has been shown to be correlated negatively with PT growth potential in hemodialysis patients with 28HPT (7,15,16). Thus, we hypothesized that VDR expression may have some link to proliferative activity in PT adenomas.…”

Section: Introductionmentioning

confidence: 99%

“…In recent studies, CaSR expression in parathyroid glands (PTGs) has been found to be decreased in cases of primary hyperparathyroidism (18HPT) and secondary hyperparathyroidism (28HPT) that were due to chronic renal failure (5,6). We and others have previously demonstrated that CaSR expression is associated not only with PTH secretion but also with parathyroid (PT) growth potential in 28HPT (7,8). However, it remains to be seen whether the CaSR is also involved in the growth potential of PT adenomas and/or clinical severity in 18HPT.…”

Section: Introductionmentioning

confidence: 99%

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Decrease in vitamin D receptor and calcium-sensing receptor in highly proliferative parathyroid adenomas

Yano

Sugimoto

Tsukamoto

et al. 2003

European Journal of Endocrinology

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Objective: A significant decrease in vitamin D receptor (VDR) and calcium-sensing receptor (CaSR) protein expression has been demonstrated recently in parathyroid (PT) adenomas. In this study, we investigated the relationships between the proliferative activity of parathyroid glands (PTGs) and the expression of VDR as well as CaSR, and compared it with the clinical severity in patients with primary hyperparathyroidism (18HPT). Design: Seven patients with 18HPT were included in this study. Four patients with thyroid carcinoma served as controls. Methods: Immunohistochemical staining was performed on serial sections of PTGs with specific antibodies against CaSR, VDR, and Ki67. Areas examined in each section were selected at random in relation to the gland size. The number of Ki67-positive cells was expressed as a labeling index (LI; positive cells per 1000 PT cells). The expression of CaSR and VDR was semi-quantitatively analyzed based on the intensity of staining. After averages of the scores from all areas were calculated, CaSR and VDR scores, and Ki67 LI were assigned to each gland for use in statistical analyses. Results: In PT adenomas, scores of VDR and CaSR were markedly lower than in normal PTGs ðP , 0:01Þ; while the proportion of Ki67-positive cells in PT adenomas was significantly higher than in normal PTGs ðP , 0:01Þ: Single regression analyses revealed that Ki67 LI was positively correlated with serum levels of intact parathyroid hormone and Ca, and PTG weight (R ¼ 0:70; P , 0:05; R ¼ 0:78; P , 0:01 and R ¼ 0:84; P , 0:05 respectively). Ki67 LI was negatively correlated with CaSR and VDR scores (R ¼ 20:78; P , 0:01 and R ¼ 20:72; P , 0:05 respectively). Moreover, there was a strong positive relationship between CaSR and VDR expression ðR ¼ 0:95; P , 0:001Þ: Conclusions: Marked decreases in VDR and CaSR expression could, at least in part, be responsible for the high proliferation of PT cells and the pathological progression of 18HPT.

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Section: Vdr and Casr Expression In Pt Adenomassupporting

confidence: 79%

Section: Immunohistochemistrymentioning

confidence: 99%

Section: Quantification Of Immunohistochemical Signalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Decrease in vitamin D receptor and calcium-sensing receptor in highly proliferative parathyroid adenomas

Yano

Sugimoto

Tsukamoto

et al. 2003

European Journal of Endocrinology

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Tumor expression of calcium sensing receptor and colorectal cancer survival: Results from the nurses’ health study and health professionals follow‐up study

Momen-Heravi

Masugi

Qian

et al. 2017

Intl Journal of Cancer

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Although experimental evidence suggests calcium-sensing receptor (CASR) as a tumor-suppressor, the prognostic role of tumor CASR expression in colorectal carcinoma remains unclear. We hypothesized that higher tumor CASR expression might be associated with improved survival among colorectal cancer patients. We evaluated tumor expression levels of CASR by immunohistochemistry in 809 incident colorectal cancer patients within the Nurses’ Health Study and the Health Professionals Follow-up Study. We used Cox proportional hazards regression models to estimate multivariable hazard ratio (HR) for the association of tumor CASR expression with colorectal cancer-specific and all-cause mortality. We adjusted for potential confounders including tumor biomarkers such as microsatellite instability, CpG island methylator phenotype, LINE-1 methylation level, expressions of PTGS2, VDR, and CTNNB1, and mutations of KRAS, BRAF, and PIK3CA. There were 240 colorectal cancer-specific deaths and 427 all-cause deaths. The median follow-up of censored patients was 10.8 years (interquartile range: 7.2, 15.1). Compared to patients with no or weak expression of CASR, the multivariable HRs for colorectal cancer-specific mortality were 0.80 [95% confidence interval (CI): 0.55-1.16] in patients with moderate CASR expression, and 0.50 (95% CI: 0.32-0.79) in patients with intense CASR expression (p-trend = 0.003). The corresponding HRs for overall mortality were 0.85 (0.64-1.13) and 0.81 (0.58-1.12), respectively. Higher tumor CASR expression was associated with a lower risk of colorectal cancer-specific mortality. This finding needs further confirmation and if confirmed, may lead to better understanding of the role of CASR in colorectal cancer progression.

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Normocalcemic primary hyperparathyroidism in patients with recurrent kidney stones: pathological analysis of parathyroid glands

et al. 2006

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The lack of overt elevation of serum calcium concentration in some patients suffering from primary hyperparathyroidism is an intriguing clinical phenomenon. Previous studies have substantiated abnormal parathyroid tissue in these patients, but the extent and mode of derangements remained largely undefined. The parathyroid tissues from patients of normocalcemic primary hyperparathyroidism (NCPHPT) and those having normal parathyroid glands, hypercalcemic primary hyperplasia, secondary hyperplasia, and adenoma were compared by undertaking quantitative immunohistochemistry analysis on tissue microarray. The statistic results suggested that the parathyroid tissue of NCPHPT approximates more to normal gland than to its counterpart in other groups of parathyroid proliferative diseases in terms of the lack of significant alterations of calcium-sensing receptor (CaSR), chromogranin A (CGA), parathyroid hormone (PTH), and proliferation index (Ki67). On the other hand, the depressed vitamin D receptor (VitDR) and elevated cyclin D1 (CyD1) of NCPHPT indicated the inherent functional abnormalities in parathyroid cells. Our results imply that inherent functional disengagement may exist between CaSR and CyD1 or between CaSR and VitDR or both in parathyroid cells of symptomatic NCPHPT. Lack of enhanced release of CGA and PTH and discordance between proliferative activity and CyD1 expression in parathyroid cells may further hinder the development of hypercalcemia.

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Association of decreased calcium-sensing receptor expression with proliferation of parathyroid cells in secondary hyperparathyroidism

Cited by 43 publications

References 1 publication

Decrease in vitamin D receptor and calcium-sensing receptor in highly proliferative parathyroid adenomas

Decrease in vitamin D receptor and calcium-sensing receptor in highly proliferative parathyroid adenomas

Tumor expression of calcium sensing receptor and colorectal cancer survival: Results from the nurses’ health study and health professionals follow‐up study

Normocalcemic primary hyperparathyroidism in patients with recurrent kidney stones: pathological analysis of parathyroid glands

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