Show simple item record

dc.contributor.authorPedersen, Kjetil Boyeen_US
dc.contributor.authorJacob, Havjinen_US
dc.contributor.authorFrikstad, Kari-Anneen_US
dc.contributor.authorNesland, Jahn Men_US
dc.contributor.authorMælandsmo, Gunhilden_US
dc.contributor.authorDahl, Olaven_US
dc.contributor.authorNesbakken, Arilden_US
dc.contributor.authorFlatmark, Kjerstien_US
dc.PublishedPedersen KB, Jacob H, Frikstad K, Nesland JM, Mælandsmo GM, Dahl O, Nesbakken A, Flatmark K. Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population-based series and a randomized phase III study on adjuvant chemotherapy. Cancer Medicine. 2016;5(8):1840-1849eng
dc.description.abstractCurrent clinical algorithms are unable to precisely predict which colorectal cancer patients would benefit from adjuvant chemotherapy, and there is a need for novel biomarkers to improve the selection of patients. The metastasis-promoting protein S100A4 predicts poor outcome in colorectal cancer, but whether it could be used to guide clinical decision making remains to be resolved. S100A4 expression was analyzed by immunohistochemistry in primary colorectal carcinomas from a consecutively collected, population-representative cohort and a randomized phase III study on adjuvant 5-fluorouracil/levamisole. Sensitivity to treatment with 5-fluorouracil in S100A4 knockdown cells was investigated using 2D and 3D cell culture assays. Strong nuclear expression of S100A4 was detected in 19% and 23% of the tumors in the two study cohorts, respectively. In both cohorts, nuclear immunoreactivity was associated with reduced relapse-free (P < 0.001 and P = 0.010) and overall survival (P = 0.046 and P = 0.006) in univariate analysis. In multivariate analysis, nuclear S100A4 was a predictor of poor relapse-free survival in the consecutive series (P = 0.002; HR 1.9), but not in the randomized study. Sensitivity to treatment with 5-fluorouracil was not affected by S100A4 expression in in vitro cell culture assays, and there was no indication from subgroup analyses in the randomized study that S100A4 expression was associated with increased benefit of adjuvant treatment with 5-fluorouracil/levamisole. The present study confirms that nuclear S100A4 expression is a negative prognostic biomarker in colorectal cancer, but the clinical utility in selection of patients for adjuvant fluoropyrimidine-based chemotherapy is limited.en_US
dc.rightsAttribution CC BYeng
dc.subjectadjuvant chemotherapyeng
dc.subjectcolorectal cancereng
dc.subjectprognostic factoreng
dc.titlePrognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population-based series and a randomized phase III study on adjuvant chemotherapyen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2016 The Author(s)
dc.source.journalCancer Medicine

Files in this item


This item appears in the following Collection(s)

Show simple item record

Attribution CC BY
Except where otherwise noted, this item's license is described as Attribution CC BY