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Published on: July 15, 2015
Assessment of cellular expression of parathyroid hormone-related protein mRNA and protein in multiple myeloma
1Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.
Abstract:
The capacity of multiple myeloma cells to generate parathyroid hormone-related protein (PTHrP) has been examined by in situ assessment of PTHrP mRNA and PTHrP protein in myeloma cells of patients in whom the disease was associated with the development of hypercalcaemia. The presence of PTHrP mRNA was evaluated by in situ hybridization using an antisense riboprobe, and PTHrP by immunohistochemistry using a monoclonal antibody, in archival bone marrow trephine specimens from 17 patients. PTHrP mRNA was detected in myeloma cells in 16 of the 17 patients, indicating a high frequency of PTHrP gene expression in myeloma cells in these subjects. PTHrP protein was, on the other hand, detected in the myeloma cells of only five of these patients. The impact of the mercury-based fixation and decalcification procedure used for processing the bone marrow trephine specimens was assessed to determine the influence of this process on the outcome of the immunohistochemical assay for PTHrP. It was shown that this preparative procedure resulted in a marked reduction of immunohistochemically detectable PTHrP, which provides a possible explanation for the lower frequency of positivity for PTHrP in myeloma cells in the bone marrow specimens. The present findings are consistent with the view that PTHrP can be generated in myeloma cells in vivo, and could contribute to osteolysis and hypercalcaemia, as in patients with cancer.
Insights
Multiple myeloma cells can produce parathyroid hormone-related protein (PTHrP), a key factor in hypercalcemia. Specimen processing significantly impacts PTHrP detection, explaining lower protein levels in patients.
Area of Science:
- Oncology
- Endocrinology
- Pathology
Background:
- Multiple myeloma is a cancer of plasma cells.
- Hypercalcemia is a common complication of multiple myeloma.
- Parathyroid hormone-related protein (PTHrP) is implicated in cancer-associated hypercalcemia.
Purpose of the Study:
- To investigate the expression of PTHrP in multiple myeloma cells.
- To determine if PTHrP produced by myeloma cells contributes to hypercalcemia.
- To assess the impact of sample preparation on PTHrP detection.
Main Methods:
- In situ hybridization to detect PTHrP mRNA in myeloma cells.
- Immunohistochemistry to detect PTHrP protein in myeloma cells.
- Analysis of archival bone marrow trephine specimens from 17 patients.
Main Results:
- PTHrP mRNA was detected in 16 out of 17 patients, indicating high gene expression.
- PTHrP protein was detected in only 5 out of 17 patients.
- Mercury-based fixation and decalcification significantly reduced detectable PTHrP protein.
Conclusions:
- Multiple myeloma cells can generate PTHrP in vivo.
- PTHrP production by myeloma cells may contribute to hypercalcemia and osteolysis.
- Sample preparation methods can affect PTHrP detection, necessitating careful consideration in diagnostic assays.
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