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CaSR expression in normal parathyroid and PHPT: new insights into pathogenesis from an autopsy-based study

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Abstract

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.

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Data availability

The data are accurate, and there is no doubt about the data’s transparency.

Code availability

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Acknowledgements

The authors wish to acknowledge the guidance of Dr. Ravinder Goswami, Professor, Department of Endocrinology and metabolism, in the conception, design, conduction of the project, as well as manuscript preparation.

Funding

The project was funded through an institute research grant, All India Institute of Medical Sciences, New Delhi (Memo No. F.5-59/IRG/2010/RS).

Author information

Authors and Affiliations

  1. Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India

    S. Agarwal, S. Kardam, M. Boruah & M. C. Sharma

  2. Department of Pathology, Lady Hardinge Medical College and Associated Hospitals, New Delhi, India

    P. Chatterjee

  3. Department of Surgical Oncology, All India Institute of Medical Sciences, Bilaspur, Himachal Pradesh, India

    C. Kumar

  4. Department of Forensic Medicine and Toxicology, All India Institute of Medical Sciences, New Delhi, India

    M. Tabin

  5. Department of Cardiac Biochemistry, All India Institute of Medical Sciences, New Delhi, India

    L. Ramakrishnan

Authors
  1. S. Agarwal
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  2. S. Kardam
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  3. P. Chatterjee
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  4. C. Kumar
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  5. M. Boruah
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  6. M. C. Sharma
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  7. M. Tabin
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  8. L. Ramakrishnan
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Contributions

SA is an endocrine pathologist. She was involved in the conceptualization of the study. She reviewed the histomorphology and immunohistochemistry results of all normal parathyroid tissues and primary hyperparathyroidism cases, selected the cases and the corresponding paraffin blocks for immunohistochemistry, and wrote and finalized the manuscript. SK helped in all the groundwork, including retrieving slides/blocks, performing immunohistochemistry, and reviewing histomorphology and immunohistochemistry results. PC contributed to reviewing histomorphology and immunohistochemistry results and editing the manuscript. CK is an endocrine surgeon. He was instrumental in the retrieval of normal parathyroid tissues from forensic autopsies. MB is a Ph.D. research scholar who helped in the collection of normal parathyroid tissues from forensic autopsies. MCS is an endocrine pathologist who helped in the conceptualization of the project and evaluation of histomorphology. MT is a faculty in the Department of Forensic Medicine who helped coordinate the collection of normal parathyroid tissues from forensic autopsies. LR is a faculty in the Department of Cardiac Biochemistry, AIIMS, New Delhi, and was involved in performing serum biochemistry tests.

Corresponding author

Correspondence to S. Agarwal.

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Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical approval

The study was approved by the Institute ethics committee, All India Institute of Medical Sciences, New Delhi (IEC-235/05.05.2017, RP-34/2017; IECPG-595/20.12.2017, RT-24/31.01.2018), and it is certified that the study was performed following the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

Consent to participate

Informed consent was obtained from the next of kin before collecting parathyroid tissue during post-mortem.

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Not applicable.

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Agarwal, S., Kardam, S., Chatterjee, P. et al. CaSR expression in normal parathyroid and PHPT: new insights into pathogenesis from an autopsy-based study. J Endocrinol Invest 45, 337–346 (2022). https://doi.org/10.1007/s40618-021-01646-w

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  • DOI: https://doi.org/10.1007/s40618-021-01646-w

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