PTH-independent hypercalcaemia and non-melanoma skin cancer.
BACKGROUND
Recently, it became more evident that skin is a target for neuroendocrine signals.


OBJECTIVE
(1) To evaluate the relationship between tumour aggressiveness and hypercalcaemia in patients with non-melanoma skin cancer; (2) to identify clinical, functional, biological alterations caused by this setting; (3) calcium redistribution from extracellular fluids to intracellular compartments; (4) to describe several molecular aspects of hypercalcaemia development.


METHODS
This study was conducted between January 2000 and May 2009 in Dermatoveneorological Center, Bucharest. From the 1232 cases that were investigated, there were 32 patients with keratoachantoma, 468 patients with basal cell carcinoma, 412 patients with squamous cell carcinoma and 320 healthy volunteers. All the patients were screened by clinical and paraclinical examinations (haematology, biochemistry, immunology). After biochemical confirmation of hypercalcaemia, patients had endocrine tests, electrocardiography and imagistic approaches. Total serum calcium was measured in extracellular fluids (serum, urine) by spectrophotometric methods. Ionized calcium was calculated depending on total serum calcium and total proteins. Corrected serum total calcium (cTCa) levels were calculated using albumin and total serum calcium levels. In tumour tissues and intact skin, calcium was assayed by physical methods of analysis: Instrumental Neutron Activation Analysis (INAA), Proton-Induced X-ray Emission (PIXE). Intact PTH was measured by ELISA.


RESULTS
PTH-independent hypercalcaemia prevalence is low in SCC patients (1.21%). Hypercalcaemia manifestations are multiple including: digestive, renal, neuromuscular, and cardiovascular abnormalities. In these patients, intact PTH (iPTH) is normal, urinary calcium is decreased, serum albumin is reduced, and calcium concentration in tumour tissue is significantly increased compared to healthy tissue.


CONCLUSIONS
PTH-independent hypercalcaemia has a low prevalence in SCC patients. Hypercalcaemia is correlated with susceptibility to develop metastases in SCC. A possible mechanism is PTHrp hypersecretion by malignant keratinocytes.
Nicolae
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Biochemistry Department, Dermatovenerological Center, Bucharest, Romania. koranik85@yahoo.com
Schipor
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D000328:Adult; D002118:Calcium / Q000097:blood / Q000652:urine; D002280:Basal Cell Carcinoma / Q000453:epidemiology* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000378:metabolism; D045604:Extracellular Fluid / Q000378:metabolism; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000453:epidemiology* / Q000378:metabolism; D007636:Keratoacanthoma / Q000453:epidemiology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010281:Parathyroid Hormone / Q000378:metabolism; D015995:Prevalence; D012383:Romania / Q000453:epidemiology; D012709:Serum Albumin / Q000378:metabolism; D012720:Severity of Illness Index; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000378:metabolism
D010281:Parathyroid Hormone; D012709:Serum Albumin; D002118:Calcium