Free serum hydroxyproline and total urinary hydroxyproline for the detection of skeletal metastasis.

Abstract

EARLY DETECTION of tumour metastasis is important for the clinical oncologist, since the therapeutic modalities may be influenced by the tumour stage. For some common tumours the first metastases are often in bone. The symptoms of skeletal metastasis either appear late or lack specificity. Various biochemical markers have been put forward for the early detection of tumours or their metastases (Coombes et al., 1977). For skeletal metastases, the isoenzymes of alkaline phosphatase were introduced into the clinical laboratory, but they did not bring the expected diagnostic advantage (Fishman & Ghosh, 1967). The collagen metabolite hydroxyproline is released mostly from bone but also from other connective tissue in adults (Laitinen, 1974). It has raised "particular hope and interest" as a marker of skeletal involvement by tumours (Reynoso, 1973). This amino acid is fairly specific for bone turnover. It is produced by hydroxylation of proline, previously integrated in the procollagen molecule (Grant & Prockop, 1972) and it is released from bone when the connective tissue is broken down in bone turnover (Klein et al., 1964). Several clinical studies have proved the relevance of total urinary hydroxyproline in the diagnosis of various disorders of bone (for review see Laitinen, 1974) and particularly in the diagnosis of skeletal metastasis of various tumours (Basu et al., 1974; Bonadonna et al., 1966; Guzzo et al., 1969; Hosley et al., 1966). Kontturi et al. (1974) have studied free serum hydroxyproline (FSHP) in prostatic carcinoma. Powles et al. (1975) have shown the value of the total urinary hydroxyproline/ creatinine ratio (HP/CR) for the evaluation of the response to a given treatment in breast cancer metastatic to the skeleton. We have planned the present study to answer to the following questions:

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