Clinical significance of prognostic and predictive markers in colorectal cancer

Longley, Daniel B.; McDermott, Ultan; Johnston, Patrick G.

doi:10.1038/sj.tpj.6500124

Cited by 12 publications

(10 citation statements)

References 54 publications

(56 reference statements)

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“…2B-E. Only LFABP (log rank = 14.4; P = 0.001), p16 (log rank = 23.9; P = 0.001), MMP9 (log rank = 8.98; P = 0.0027), and TIMP3 (log rank = 4.05; P = 0.04) displayed prognostic significance in the whole cohort of patients. The median survival in the LFABP high group (n = 4) was 9 months (95% CI, 0-19; mean, 11 months; 95% CI, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19], whereas in the LFABP low group (n = 86) the median survival was 43 months (95% CI, 26-60; mean, 55 months; 95% CI, 47-63). In the p16 z50% group (n = 8), the median survival was 10 months (95% CI, 6-14; mean, 20 months; 95% CI, , whereas in the p16 <50% group (n = 82) the median survival was 48 months (95% CI, 27-69; mean, 56 months; 95% CI, 48-65).…”

Section: Resultsmentioning

confidence: 99%

Profiling markers of prognosis in colorectal cancer.

Lyall

Dundas

Curran

et al. 2006

Clinical Cancer Research

108

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Purpose: Colorectal cancer is one of the most common forms of cancer in developed nations and the incidence of this disease is increasing. There is a need to further stratify prognostically distinct groups of colorectal cancer, and the purpose of this study was to identify prognostically significant immunohistochemical marker profiles in colorectal cancer. Experimental Design: In this study, a range (n = 23) of markers [pRb, p16, p21, p27, p53, proliferating cell nuclear antigen, cyclin D1, bcl-2, epidermal growth factor receptor, C-erb-B2, topoisomerase-I, liver fatty acid^binding protein, matrix metalloproteinases (MMP) 1-3, 7, 9, and 13, MT1-MMP, MT2-MMP, and tissue inhibitors of MMP 1-3] of putative prognostic significance have been investigated by immunohistochemistry on formalin-fixed, wax-embedded sections in a series (n = 90) of stage III (Dukes C) colorectal cancers. An immunohistochemical score based on the intensity of immunoreactivity and, where relevant, the proportion of immunoreactive cells was established for each marker. Results: Unsupervised two-dimensional hierarchical cluster analysis identified three distinct cluster groups (designated groups 1-3) with different marker profiles. There were significant survival differences between groups 1and 2 (log rank = 11.48; P = 0.0007) and between groups 1and 3 (log rank = 8.32; P = 0.0039). Multivariate analysis showed that the complete marker profile was independently the most significant prognostic factor (hazard ratio, 2.27; 95 % confidence interval, 1.15-4.48; P = 0.004). Conclusions: This study has identified an immunohistochemical marker profile of colorectal cancer and showed that it is an independent indicator of prognosis in this type of cancer.

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Section: Resultsmentioning

confidence: 99%

Profiling markers of prognosis in colorectal cancer.

Lyall

Dundas

Curran

et al. 2006

Clinical Cancer Research

108

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“…Furthermore, a number of clinical studies have found that p53 mutations correlated with resistance to 5-FU, although other studies found no such association (34). We assessed the effect of p53 inactivation on drug-induced Fas-mediated apoptosis in two p53 wild-type and p53-null isogenic cell line pairs: the MCF-7-derived M7TS90 and M7TS90-E6 cell lines; and the HCT116 p53 ϩ/ϩ and HCT116 p53 Ϫ/Ϫ cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, preclinical and clinical studies have found that TS is a key determinant of sensitivity to 5-FU, with high TS expression correlating with increased resistance (1,34). We therefore examined the effect of elevated TS expression on activation of Fas-mediated apoptosis in 5-FU-and antifolate-treated cells using a tetracycline-regulated TS expression system (M7TS90).…”

Section: Discussionmentioning

confidence: 99%

The Roles of Thymidylate Synthase and p53 in Regulating Fas-Mediated Apoptosis in Response to Antimetabolites

Longley¹,

Allen²,

McDermott³

et al. 2004

Clinical Cancer Research

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“…However, many studies of TS expression have used immunohistochemistry. The immunohistochemical method presents several limitations for evaluation of the TS expression, including observer variation and lack of standardization [10,26]. Our study did not demonstrate a significant correlation between TS immunoexpression and survival.…”

Section: Discussionmentioning

confidence: 88%