Serum cross-linked carboxyterminal telopeptide of type I collagen (ICTP) as a prognostic tumor marker in patients with esophageal squamous cell carcinoma.
BACKGROUND
Serum cross-linked carboxyterminal telopeptide of Type I collagen (ICTP) is a metabolite of Type I collagen and has been reported to serve not only as a marker of bone metastasis but also as an indicator of treatment response and prognosis in several malignant tumors. The objective of this work was to evaluate the value of serum ICTP as a tumor marker in patients with esophageal squamous cell carcinoma (SCC).


METHODS
In this study, pretreatment serum ICTP concentrations were measured by double-antibody radioimmunoassay in 50 patients undergoing tumor resection, chemoradiotherapy, or palliation for newly diagnosed esophageal SCC. The cutoff value for positive ICTP levels was defined as 4.50 ng/mL. As a comparison, serum concentrations of SCC antigen, carcinoembryonic antigen, cytokeratin-19 fragment, alkaline phosphatase, and lactate dehydrogenase were simultaneously evaluated. The results were categorized according to several clinicopathologic variables.


RESULTS
Among the markers tested, ICTP showed the highest sensitivity (58.0%) in esophageal SCC sera. Positive ICTP levels were significantly correlated with tumor progression variables, such as tumor depth > or = T2, regional lymph node metastasis (N1), distant metastasis (M1), TNM stage > or = II, and maximal tumor length greater than 50 mm. Survival analyses of 29 patients who underwent curative resection demonstrated that patients who were positive for ICTP had significantly worse outcomes in terms of overall, disease specific, and disease free survival than those who were negative. Multivariate analyses confirmed that serum ICTP levels provided an independent prognostic indicator of overall and disease specific survival. However, serum ICTP values did not correlate with prognosis or treatment response in 17 unresectable cases treated by chemoradiotherapy.


CONCLUSIONS
Our results indicated that serum ICTP concentrations might be a novel prognostic tumor marker for assessing the progression of esophageal SCC.
Nabeya
Yoshihiro
Y
Department of Academic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. nabeya-y@srgy201.m.chiba-u.ac.jp
Shimada
Hideaki
H
Okazumi
Shinichi
S
Matsubara
Hisahiro
H
Gunji
Yoshio
Y
Suzuki
Takao
T
Ochiai
Takenori
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D024042:Collagen Type I / Q000097:blood* / Q000378:metabolism*; D003432:Cross-Linking Reagents; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D011863:Radioimmunoassay; D012680:Sensitivity and Specificity; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D024042:Collagen Type I; D003432:Cross-Linking Reagents; D010446:Peptide Fragments; D011347:Procollagen; C042813:procollagen type I carboxy terminal peptide