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| Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2013 Dec 6. pii: modpathol2013204. doi: 10.1038/modpathol.2013.204 |
| Differential survival trends of stage II colorectal cancer patients relate to promoter methylation status of PCDH10, SPARC, and UCHL1. |
| Heitzer E1, Artl M2, Filipits M3, Resel M4, Graf R5, Weißenbacher B6, Lax S7, Gnant M8, Wrba F9, Greil R10, Dietze O11, Hofbauer F12, Böhm G13, Höfler G14, Samonigg H15, Schaberl-Moser R16, Balic M17, Dandachi N18 |
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Abstract Surgical excision of colorectal cancer at early clinical stages is highly effective, but 20-30% of patients relapse. Therefore, it is of clinical relevance to identify patients at high risk for recurrence, who would benefit from adjuvant chemotherapy. The objective of this study was to identify prognostic and/or predictive methylation markers in stage II colorectal cancer patients. Therefore, we selected six gene promoters (FZD9, PCDH10 (protocadherin 10), SFRP2, SPARC (secreted protein acidic and rich in cysteine), UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), and WIF1) for methylation analysis in formalin-fixed, paraffin-embedded primary tumor samples of colorectal cancer patients (n=143) who were enrolled in a prospective randomized phase III trial of the Austrian Breast and Colorectal cancer Study Group. Patients were randomized to adjuvant chemotherapy with 5-fluorouracil and leucovorin or surveillance only. Survival analyses revealed that combined evaluation of three promoters (PCDH10, SPARC, and UCHL1) showed differential effects with regard to disease-free survival and overall survival in the two treatment groups (significance level 0.007). In the chemotherapy arm, a statistically insignificant trend for patients without methylation toward longer survival was observed (P=0.069 for disease-free survival and P=0.139 for overall survival). Contrary, patients in the surveillance arm without methylation in their gene promoters had shorter disease-free survival and overall survival (P=0.031 for disease-free survival and P=0.003 for overall survival), indicating a prognostic effect of methylation in this group (test for interaction, P=0.006 for disease-free survival and P=0.018 for overall survival). These results indicate that promoter methylation status of PCDH10, SPARC, and UCHL1 may be used both as prognostic and predictive molecular marker for colorectal cancer patients and, therefore, may facilitate treatment decisions for stage II colorectal cancer. |
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Publikations ID: 24309322 Quelle: öffnen |
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