Overexpression of collagen XVIII is associated with poor outcome and elevated levels of circulating serum endostatin in non-small cell lung cancer.
OBJECTIVE
The aim of this study was to determine whether collagen XVIII expression is correlated with circulating serum endostatin and whether this has any prognostic value in patients with non-small cell lung cancer (NSCLC).


METHODS
Serum endostatin levels were measured quantitatively by a competitive enzyme immunoassay, and collagen XVIII expression in tumor tissue was investigated with an immunohistochemical method in a series of 94 patients who underwent surgery for NSCLC.


RESULTS
Sixty cases (63.8%) had positive immunohistochemical staining with anticollagen XVIII polyclonal antibodies, including strongly positive staining in 11 (11.7%) cases. The mean (+/- SD) serum endostatin level was 41.6 +/- 34.4 ng/ml in the patient group and 16.3 +/- 10.3 ng/ml in the control group (P < 0.0001). The 11 cases who were strongly collagen XVIII-positive had significantly higher serum endostatin levels than the cases who were negative or weakly positive (P = 0.0297). The 5-year survival rates of negative, weakly positive, and strongly positive patients were 77.8%, 56.9%, and 43.8%, respectively. The cases with strongly positive collagen XVIII expression had a significantly poorer outcome than cases with negative expression (P = 0.0027). A multivariate analysis with Cox proportional hazards model for disease-specific survival revealed that expression of collagen XVIII (strongly positive versus negative; weakly positive versus negative), tumor classification, and regional lymph node classification were independent prognostic factors.


CONCLUSIONS
Our results suggest that expression of collagen XVIII in tumor tissue is strongly associated with a poorer outcome in NSCLC and correlates with elevated levels of circulating serum endostatin.
Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Toshihiko
T
Iizasa
Hao
H
Chang
Makoto
M
Suzuki
Mizuto
M
Otsuji
Sana
S
Yokoi
Masako
M
Chiyo
Shinichiro
S
Motohashi
Kazuhiro
K
Yasufuku
Yasuo
Y
Sekine
Akira
A
Iyoda
Kiyoshi
K
Shibuya
Kenzo
K
Hiroshima
Takehiko
T
Fujisawa
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D043170:Collagen Type XVIII / Q000378:metabolism*; D043169:Endostatins / Q000097:blood*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D017211:Treatment Failure; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D043170:Collagen Type XVIII; D043169:Endostatins