Follow-up of collagen crosslink excretion in patients with oral squamous cell carcinoma and analysis of tissue samples

Abstract

The presence of an oral squamous cell carcinoma (OSCC) may be associated with increased urinary excretion of the markers of collagen degradation, hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP). We investigated the possibility of these markers predicting the presence of active disease. Patients from a current study on HP and LP were included as follows: Group 1a (OSCC with confirmed mandibular bony infiltration, n ¼ 12), group 1b (group 1a patients 46 months after successful treatment), group 2a (OSCC without evidence of mandibular bone infiltration, n ¼ 8), group 2b (group 2a patients 46 months after successful treatment), group 3a (recurrent OSCC, n ¼ 8), group 3b (group 3a patients 46 weeks later, symptoms unchanged) and group 4 (control group, n ¼ 74). Tissue samples from tumour tissue and adjacent healthy mucosa were additionally investigated for HP and LP concentrations (n ¼ 8). The decrease in the urinary concentrations of HP and LP was statistically significant between groups 1a and 1b (Po0.001 for HP and LP), but not between groups 2a and 2b (P ¼ 0.07 for HP and LP), while values in groups 1b and 2b were within the normal range. When comparing groups 3a and 3b, a significant increase was observed for LP (P ¼ 0.050), but not HP (P ¼ 0.208). In conclusion, successful treatment of OSCC with bony involvement may be associated with a reduction of urinary HP and LP, whereas ongoing disease may result in an increase of LP. HP and LP may both be useful markers of tumour progression in patients with OSCC. British Journal of Cancer (2003) Hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are two nonreducible crosslinks of mature collagen, which are formed by a sequence of post-translational modifications. HP is a derivative of three residues of hydroxylysine, and is present in virtually all mature tissues (tendon, vessel wall, cartilage, dentine and bone). LP is a derivative of two residues of hydroxylysine and one residue of lysine, and is found primarily in dentine and bone (Body and Delmas, 1992;Eyre, 1992;Miyamoto et al, 1994;Acil et al, 1996Acil et al, , 2002aPapatheofanis, 1997;Tamada et al, 2001;Jepsen et al, 2003; Springer et al, 2003a, b).It has been suggested that the detection of LP in the serum or urine may be a helpful marker in establishing and possibly quantifying bone matrix resorption (Body and Delmas, 1992;Miyamoto et al, 1994;Vinholes et al, 1996;Papatheofanis, 1997;Tamada et al, 2001;Springer et al, 2003a). In a previous study, we were able to assess the range and upper limit (HP max and LP max ) of normal values. We were able to show that the measurement of LP in the urine was able to separate a group of patients with oral squamous cell carcinoma (OSCC) with bone infiltration from patients with OSCC without bone infiltration with a sensitivity of 100% and a specificity of 100% (Springer et al, 2003a). In that paper, we suggested that when the level of LP exceeds LP max in a patient with a confirmed OSCC, bony invasion by the malignant process is highly likely and further inve...

The use of molecular markers of bone turnover in the management of patients with metastatic bone disease

“…Not surprisingly, the available information on the diagnostic use of bone markers in metastatic bone disease is heterogeneous and often incongruent. The picture becomes more consistent when comparisons are made between a marker of bone turnover and specific imaging techniques, namely bone radioisotopes scans, or surgical outcomes in well‐defined groups of patients 8–11 …”

“…The picture becomes more consistent when comparisons are made between a marker of bone turnover and specific imaging techniques, namely bone radioisotopes scans, or surgical outcomes in well-defined groups of patients. [8][9][10][11] Of the available bone formation markers (Table 1), serum total (TAP) and bone-specific alkaline phosphatase (BAP) usually exhibit the most pronounced changes in response to metastatic bone involvement. In most cases of advanced cancers metastatic to bone, serum TAP and BAP levels are elevated, pointing to either a strong osteoblastic component or, in lytic lesions, to active repair.…”

“…The majority of patients with breast, prostate, lung or oral squamous cell cancers metastatic to bone exhibited abnormally high urinary levels of the collagen crosslink, deoxypyridinoline (DPD). 11,[25][26][27][28] In some studies (e.g. Pecherstorfer et al .…”

A new method of monitoring osteomyelitis

“…Urinary HP and LP concentrations are valuable markers of the progression of diseases characterized by altered bone absorption even if located solely in the mandible 28 . This study indicates that osteomyelitis is now on this list.…”