Justine Southby

Immunohistochemical localization of parathyroid hormone-related protein in the lesions of breast disease

Parathyroid hormone-related protein (PTHrP) is a major contributing factor in the aetiology of humoral hypercalcaemia of malignancy (HHM). HHM is often a complication of squamous cell carcinoma of the bronchus but may occur with tumours of other epithelial surfaces. Hypercalcaemia occurs in 10% of patients with advanced breast cancer and a breast rumour cell line has been a source of PTHrP (Stewart el al ., 1987, BBRC 146:672-8). Polyclonal antibodies have been raised in rabbits against synthetic (1-34) peptides. This antiserum is highly specific and does not cross-react with PTH on Western blot, in radioimmunoassay or at high concentrations to block adenylate cyclase in PTH responsive cells. Using this antiserum and peroxidase antiperoxidase procedures PTHrP has been identified in breast lesions. A range of normal and lactating breast tissues and pathological lesions of the breast have been examined. PTHrP staining is absent from normal resting and lactating breast tissue, from the lesions of fibrocystic disease, absent in gynaecomastia and in most fibroadenomas. It has been shown to be present in one fibroadenoma with evidence of secretory activity, where the protein appeared to be associated with secretory vacuoles. In a patient with hypercalcaemia occurring with giant hypertrophy of both breasts the protein was present in myoepithelial cells and so called “clear” or stem cells of the ducts. In duct carcinoma the protein has been shown to be present within clumps or cords of tumour cells, particularly in those areas which have foci of microcalcification. In medullary carcinoma PTHrP staining occurs within the “crushed” cells, described by Azzopardi, occurring around the margin of tumour cords. Demonstration of the PTHrP antigen in malignant breast tumour tissue provides an explanation for the association of HHM with these tumours. It is possible that the hormone may also be at least in part responsible for the ability of these tumours to resorb and to metastasise to bone