In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 3597-3597
Abstract:
3597 Background: Tight junctions (TJ) are the most apical epithelial cell–cell adhesions. Claudin super-family trans-membrane proteins, including claudin 2 (cl2), are important components of TJs. Expression of cl2 has been reported to be elevated in colorectal cancer (CRC) and its up-regulation increases tumorigenicity of CRC cells in vitro. The aim of this study was to analyze the prognostic significance of cl2 in CRC. Methods: A tissue microarray (TMA) from the stage IV CRC patients of the phase III NORDIC-VII study was used. Cl2 IHC staining was evaluated in a semi-quantitative manner in cancer cells (cl2-C) and in the tumor stroma (cl2-S). Primary fibroblasts were established from human CRC tumor tissue and non-tumor colon tissue, and evaluated by immunoblotting. Results: Analyses of the TMA derived from the NORDIC-VII cohort revealed that cancer cell expression and tumor stroma expression of cl2 was associated with shorter OS in a Log-Rank test for trend (cl2-C, n=315, p=0.018; cl2-S, n=319, p=0.020). Expression of cl2-S, but not cl2-C was prognostic in multivariate analysis including WHO performance status, alkaline phosphatase level and BRAF mutation status (HR=1.30; 95% CI 1.08-1.56; p=0.006). When cl2-C and cl2-S expression was combined the prognostic significance was increased. The group with high cl2-C and high cl2-S (N=182), when compared with the rest of the cases (n=129), displayed a worse prognosis in terms of OS (19.1 mo vs 27.2 mo; p=0.003) in univariate analyses (HR=1.55, 95% CI 1.16-2.08, p=0.003) and in multivariate analyses (HR=1.52, 95% CI 1.13-2.05, p=0.006). Immunoblotting analysis of primary cultures of fibroblasts confirmed cl2 expression in fibroblasts from CRC tissue and from non-tumor tissue, with higher expression observed in the tumor fibroblasts. Conclusions: CRC display a previously un-reported stromal expression of cl2 of prognostic significance. High cl2-S is associated with worse prognosis in patients with metastatic CRC, in a manner independent of WHO status, alkaline phosphatase levels and BRAF status. Furthermore, high expression of cl2 in both cancer cells and the tumor stroma is also associated with poor prognosis.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.3597
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
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