Increased expression of collagen XVIII and its prognostic value in nonsmall cell lung carcinoma

Hao Chang, Toshihiko Iizasa, Kiyoshi Shibuya, Akira Iyoda, Makoto Suzuki, Yasumitsu Moriya, Tian-Ling Liu, Takaki Hiwasa, Kenzo Hiroshima, Takehiko Fujisawa
Cancer 2004 April 15, 100 (8): 1665-72

BACKGROUND: Angiogenesis plays a crucial role in tumor growth and metastasis. Recently, some studies have focused on the angiogenesis inhibitor endostatin. However, the biologic role of the precursor of endostatin, collagen XVIII, in human malignancy is unknown. The purpose of the current study was to evaluate whether the expression of collagen XVIII has additional prognostic value for survival in patients with nonsmall cell lung carcinoma (NSCLC).

METHODS: The authors investigated the expression of collagen XVIII in 221 patients using immunohistochemical methods. To confirm the specificity of the collagen XVIII polyclonal antibody used in the current study and to test the expression of collagen XVIII in human lung carcinoma, Western blot analysis was performed on a panel of human lung carcinoma cell lines.

RESULTS: Collagen XVIII expression was detected in 162 of 221 patients with NSCLC (73%), primarily in the tumor cell cytoplasm. Low collagen XVIII expression levels were found in 75 tumor specimens, while high collagen XVIII expression levels were noted in 87 tumor specimens. The prevalence of positive collagen XVIII expression was greater in T2-4 tumors than in T1 tumors (P = 0.0235). The prognosis for patients with strongly collagen XVIII-positive NSCLC was significantly worse than the prognosis for patients with collagen XVIII-positive or collagen XVIII-negative NSCLC (P = 0.0010). Multivariate analysis indicated that T status, lymph node status, and the overexpression of collagen XVIII were independent prognostic factors.

CONCLUSIONS: The results of the current study indicated that the overexpression of collagen XVIII was associated with NSCLC progression and poor outcome. Thus, collagen XVIII expression may serve as a useful prognostic marker in patients with NSCLC.

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