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Collagen crosslink excretion and staging of oral cancer.

Springer IN, Terheyden H, Dunsche A, Czech N, Suhr MA, Tiemann M, Hedderich J, Açil Y - Br. J. Cancer (2003)

Bottom Line: There was a significant difference in the average urinary levels of LP and HP between groups 1-4 (P<0.001).Presence of tumour tissue could be detected with a sensitivity of 90%.In conclusion, a normal LP concentration in patients with an OSCC strongly suggests that bone invasion by the disease has not taken place.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral and Maxillofacial Surgery, University of Kiel, Germany. springer@mkg.uni-kiel.de

ABSTRACT
Lysylpyridinoline (LP) and hydroxylysylpyridinoline (HP) are collagen crosslink residues of which the urinary concentration reflects the level of connective-tissue turnover. HP is ubiquitous in tissue, whereas LP is specific for bone. The purpose of this investigation was to assess the sensitivity and specificity of an increased urinary concentration of both HP and LP in indicating infiltration of mandibular bone by an oral squamous cell carcinoma (OSCC) or recurrence of the disease after successful therapy. We investigated the history and urine levels in 116 adult patients, who were divided into the following groups. Group 1: patients with OSCC with bone infiltration (n=17); group 2: patients with confirmed OSCC (n=12) without evidence of bone infiltration; group 3: patients with recurrence of an OSCC (n=13); group 4: patients without clinical evidence of disease (n=74). The range and upper limit of normal values (HP(max) and LP(max)) were measured from the normal controls in group 4. Levels of LP and HP were measured by HPLC and fluorescence detection. There was a significant difference in the average urinary levels of LP and HP between groups 1-4 (P<0.001). The presence of mandibular bone infiltration could be detected with a sensitivity and specificity of 100% when comparing groups 1 and 2. Presence of tumour tissue could be detected with a sensitivity of 90%. In conclusion, a normal LP concentration in patients with an OSCC strongly suggests that bone invasion by the disease has not taken place. If both urinary HP and LP are elevated, disease recurrence is highly likely.

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(A) Arithmetic means of concentrations of urinary HP and LP: in groups 1 (OSCC with mandibular bone infiltration, n=17), 2 (OSCC without mandibular bone infiltration, n=12), 3 (recurrence of OSCC, n=13) and 4 (control group, n=74). Dotted lines mark HPmax (95 nmol mmol−1 creatinine) and LPmax (20 nmol mmol−1 creatinine). The urinary levels of HP in groups 1–3 are significantly different from group 4. The urinary concentrations of LP in groups 1 and 3 are significantly different from group 4. Moreover, in groups 1 and 3, the average urinary content of HP and LP exceeded HPmax and LPmax significantly. Please note that in group 2, HP is significantly elevated as a marker of increased tissue turnover as compared to group 4, but does not exceed HPmax. Length of vertical bars: standard deviation times 1.96. (B) Medians of concentrations of urinary HP and LP: Each box shows the median, quartiles and extreme values of groups 1 (OSCC with mandibular bone infiltration, n=17), 2 (OSCC without mandibular bone infiltration, n=12), 3 (recurrence of OSCC, n=13) and 4 (control group, n=74). Lines mark HPmax (95 nmol mmol−1 creatinine) and LPmax (20 nmol mmol−1 creatinine). The urinary levels of HP in groups 1–3 are significantly different from group 4. The urinary concentrations of LP in groups 1 and 3 are significantly different from group 4. Moreover, in groups 1 and 3, the urinary content of HP and LP exceeded HPmax and LPmax, significantly. As regards groups 1 and 2, the LPmax line is separating LP values, completely. O and * label values of one patient, which significantly exceeded the normal range in the recurrence group.
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fig1: (A) Arithmetic means of concentrations of urinary HP and LP: in groups 1 (OSCC with mandibular bone infiltration, n=17), 2 (OSCC without mandibular bone infiltration, n=12), 3 (recurrence of OSCC, n=13) and 4 (control group, n=74). Dotted lines mark HPmax (95 nmol mmol−1 creatinine) and LPmax (20 nmol mmol−1 creatinine). The urinary levels of HP in groups 1–3 are significantly different from group 4. The urinary concentrations of LP in groups 1 and 3 are significantly different from group 4. Moreover, in groups 1 and 3, the average urinary content of HP and LP exceeded HPmax and LPmax significantly. Please note that in group 2, HP is significantly elevated as a marker of increased tissue turnover as compared to group 4, but does not exceed HPmax. Length of vertical bars: standard deviation times 1.96. (B) Medians of concentrations of urinary HP and LP: Each box shows the median, quartiles and extreme values of groups 1 (OSCC with mandibular bone infiltration, n=17), 2 (OSCC without mandibular bone infiltration, n=12), 3 (recurrence of OSCC, n=13) and 4 (control group, n=74). Lines mark HPmax (95 nmol mmol−1 creatinine) and LPmax (20 nmol mmol−1 creatinine). The urinary levels of HP in groups 1–3 are significantly different from group 4. The urinary concentrations of LP in groups 1 and 3 are significantly different from group 4. Moreover, in groups 1 and 3, the urinary content of HP and LP exceeded HPmax and LPmax, significantly. As regards groups 1 and 2, the LPmax line is separating LP values, completely. O and * label values of one patient, which significantly exceeded the normal range in the recurrence group.

Mentions: There was no statistically significant difference between the sexes, and a normal distribution of the urinary concentrations of HP and LP was seen in groups 1–4. An analysis of variance (ANOVA) was performed to evaluate statistically significant differences between groups 1–4. Multiple comparisons were performed according to Games-Howell. Since the variance of groups 1–4 appeared to be not strictly homogeneous (Figure 1A and BFigure 1


Collagen crosslink excretion and staging of oral cancer.

Springer IN, Terheyden H, Dunsche A, Czech N, Suhr MA, Tiemann M, Hedderich J, Açil Y - Br. J. Cancer (2003)

(A) Arithmetic means of concentrations of urinary HP and LP: in groups 1 (OSCC with mandibular bone infiltration, n=17), 2 (OSCC without mandibular bone infiltration, n=12), 3 (recurrence of OSCC, n=13) and 4 (control group, n=74). Dotted lines mark HPmax (95 nmol mmol−1 creatinine) and LPmax (20 nmol mmol−1 creatinine). The urinary levels of HP in groups 1–3 are significantly different from group 4. The urinary concentrations of LP in groups 1 and 3 are significantly different from group 4. Moreover, in groups 1 and 3, the average urinary content of HP and LP exceeded HPmax and LPmax significantly. Please note that in group 2, HP is significantly elevated as a marker of increased tissue turnover as compared to group 4, but does not exceed HPmax. Length of vertical bars: standard deviation times 1.96. (B) Medians of concentrations of urinary HP and LP: Each box shows the median, quartiles and extreme values of groups 1 (OSCC with mandibular bone infiltration, n=17), 2 (OSCC without mandibular bone infiltration, n=12), 3 (recurrence of OSCC, n=13) and 4 (control group, n=74). Lines mark HPmax (95 nmol mmol−1 creatinine) and LPmax (20 nmol mmol−1 creatinine). The urinary levels of HP in groups 1–3 are significantly different from group 4. The urinary concentrations of LP in groups 1 and 3 are significantly different from group 4. Moreover, in groups 1 and 3, the urinary content of HP and LP exceeded HPmax and LPmax, significantly. As regards groups 1 and 2, the LPmax line is separating LP values, completely. O and * label values of one patient, which significantly exceeded the normal range in the recurrence group.
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Related In: Results  -  Collection

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fig1: (A) Arithmetic means of concentrations of urinary HP and LP: in groups 1 (OSCC with mandibular bone infiltration, n=17), 2 (OSCC without mandibular bone infiltration, n=12), 3 (recurrence of OSCC, n=13) and 4 (control group, n=74). Dotted lines mark HPmax (95 nmol mmol−1 creatinine) and LPmax (20 nmol mmol−1 creatinine). The urinary levels of HP in groups 1–3 are significantly different from group 4. The urinary concentrations of LP in groups 1 and 3 are significantly different from group 4. Moreover, in groups 1 and 3, the average urinary content of HP and LP exceeded HPmax and LPmax significantly. Please note that in group 2, HP is significantly elevated as a marker of increased tissue turnover as compared to group 4, but does not exceed HPmax. Length of vertical bars: standard deviation times 1.96. (B) Medians of concentrations of urinary HP and LP: Each box shows the median, quartiles and extreme values of groups 1 (OSCC with mandibular bone infiltration, n=17), 2 (OSCC without mandibular bone infiltration, n=12), 3 (recurrence of OSCC, n=13) and 4 (control group, n=74). Lines mark HPmax (95 nmol mmol−1 creatinine) and LPmax (20 nmol mmol−1 creatinine). The urinary levels of HP in groups 1–3 are significantly different from group 4. The urinary concentrations of LP in groups 1 and 3 are significantly different from group 4. Moreover, in groups 1 and 3, the urinary content of HP and LP exceeded HPmax and LPmax, significantly. As regards groups 1 and 2, the LPmax line is separating LP values, completely. O and * label values of one patient, which significantly exceeded the normal range in the recurrence group.
Mentions: There was no statistically significant difference between the sexes, and a normal distribution of the urinary concentrations of HP and LP was seen in groups 1–4. An analysis of variance (ANOVA) was performed to evaluate statistically significant differences between groups 1–4. Multiple comparisons were performed according to Games-Howell. Since the variance of groups 1–4 appeared to be not strictly homogeneous (Figure 1A and BFigure 1

Bottom Line: There was a significant difference in the average urinary levels of LP and HP between groups 1-4 (P<0.001).Presence of tumour tissue could be detected with a sensitivity of 90%.In conclusion, a normal LP concentration in patients with an OSCC strongly suggests that bone invasion by the disease has not taken place.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral and Maxillofacial Surgery, University of Kiel, Germany. springer@mkg.uni-kiel.de

ABSTRACT
Lysylpyridinoline (LP) and hydroxylysylpyridinoline (HP) are collagen crosslink residues of which the urinary concentration reflects the level of connective-tissue turnover. HP is ubiquitous in tissue, whereas LP is specific for bone. The purpose of this investigation was to assess the sensitivity and specificity of an increased urinary concentration of both HP and LP in indicating infiltration of mandibular bone by an oral squamous cell carcinoma (OSCC) or recurrence of the disease after successful therapy. We investigated the history and urine levels in 116 adult patients, who were divided into the following groups. Group 1: patients with OSCC with bone infiltration (n=17); group 2: patients with confirmed OSCC (n=12) without evidence of bone infiltration; group 3: patients with recurrence of an OSCC (n=13); group 4: patients without clinical evidence of disease (n=74). The range and upper limit of normal values (HP(max) and LP(max)) were measured from the normal controls in group 4. Levels of LP and HP were measured by HPLC and fluorescence detection. There was a significant difference in the average urinary levels of LP and HP between groups 1-4 (P<0.001). The presence of mandibular bone infiltration could be detected with a sensitivity and specificity of 100% when comparing groups 1 and 2. Presence of tumour tissue could be detected with a sensitivity of 90%. In conclusion, a normal LP concentration in patients with an OSCC strongly suggests that bone invasion by the disease has not taken place. If both urinary HP and LP are elevated, disease recurrence is highly likely.

Show MeSH
Related in: MedlinePlus