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CaSR expression in normal parathyroid and PHPT: new insights into pathogenesis from an autopsy-based study.
Journal of Endocrinological Investigation ( IF 5.4 ) Pub Date : 2021-07-24 , DOI: 10.1007/s40618-021-01646-w
S Agarwal 1 , S Kardam 1 , P Chatterjee 2 , C Kumar 3 , M Boruah 1 , M C Sharma 1 , M Tabin 4 , L Ramakrishnan 5
Affiliation  

PURPOSE Calcium sensing receptor (CaSR), on the surface of normal parathyroid cells, is essential for maintaining serum calcium levels. The normal pattern of CaSR immunostaining remains undefined and is presumptively circumferential. Given the physiological variation in serum calcium, we postulated that CaSR expression could not be uniformly circumferential. Also, cytoplasmic expression has not been evaluated either in normal or pathological tissues. We studied normal parathyroid tissues derived from forensic autopsies and those rimming parathyroid adenomas for membranous and cytoplasmic CaSR immunoexpression. Results were compared with primary hyperparathyroidism (PHPT) to look for any pathogenetic implications. MATERIALS AND METHODS We evaluated 34 normal parathyroid tissues from 11 autopsies, 30 normal rims, 45 parathyroid adenoma, 10 hyperplasia, and 7 carcinoma cases. Membranous expression was categorized complete/incomplete and weak/moderate/strong; scored using Her2/Neu and Histo-scores; predominant pattern noted. Cytoplasmic expression was categorized negative/weak/moderate/strong; predominant intensity noted. RESULTS Normal autopsy-derived parathyroid tissues were Her2/Neu 3 + , but incomplete membranous staining predominated in 85%. Their immune-scores were significantly more than the cases (p <  < 0.05). The mean histo-score of normal rims was intermediate between the two (p <  < 0.05). Cytoplasmic expression was strong in all autopsy-derived tissues, weak/negative in hyperplasia (100%), moderate in 16% adenomas, and 43% carcinomas. CONCLUSIONS Normal autopsy-derived parathyroid tissues showed strong but predominantly incomplete membranous expression. Surface CaSR expression decreased in PHPT and is probably an early event in parathyroid adenoma, seen even in normal rims. Whether there is a defect in CaSR trafficking from the cytoplasm to the cell surface in adenoma and carcinoma needs further evaluation.

中文翻译:

正常甲状旁腺和 PHPT 中的 CaSR 表达:基于尸检的研究对发病机制的新见解。

目的 正常甲状旁腺细胞表面的钙敏感受体 (CaSR) 对维持血清钙水平至关重要。CaSR 免疫染色的正常模式仍未确定,并且推测是环形的。鉴于血清钙的生理变化,我们假设 CaSR 表达不可能是均匀的圆周。此外,尚未在正常或病理组织中评估细胞质表达。我们研究了取自法医尸检的正常甲状旁腺组织和那些边缘的甲状旁腺腺瘤的膜和细胞质 CaSR 免疫表达。将结果与原发性甲状旁腺功能亢进 (PHPT) 进行比较,以寻找任何致病意义。材料和方法 我们评估了来自 11 个尸检的 34 个正常甲状旁腺组织,30 个正常边缘,45 个甲状旁腺腺瘤,增生10例,癌7例。膜表达分为完全/不完全和弱/中/强;使用 Her2/Neu 和 Histo-scores 评分;注意到的主要模式。细胞质表达分为阴性/弱/中/强;注意到主要强度。结果正常尸检衍生的甲状旁腺组织为Her2/Neu 3 +,但不完全膜染色占85%。他们的免疫评分显着高于病例(p < < 0.05)。正常轮辋的平均组织得分介于两者之间(p < < 0.05)。在所有尸检来源的组织中,细胞质表达都很强,在增生组织中表达较弱/阴性(100%),在 16% 的腺瘤和 43% 的癌中表达中度。结论 正常尸检衍生的甲状旁腺组织表现出强烈但主要是不完整的膜表达。PHPT 中表面 CaSR 表达下降,可能是甲状旁腺腺瘤的早期事件,即使在正常轮辋中也可见。在腺瘤和癌中,CaSR 从细胞质到细胞表面的运输是否存在缺陷需要进一步评估。
更新日期:2021-07-24
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