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Ref Type Journal Article
PMID (19478385)
Authors Mesker WE, Liefers GJ, Junggeburt JM, van Pelt GW, Alberici P, Kuppen PJ, Miranda NF, van Leeuwen KA, Morreau H, Szuhai K, Tollenaar RA, Tanke HJ
Title Presence of a high amount of stroma and downregulation of SMAD4 predict for worse survival for stage I-II colon cancer patients.
Journal Cellular oncology : the official journal of the International Society for Cellular Oncology
Vol 31
Issue 3
Date 2009
URL
Abstract Text For stage I-II colon cancer a significant number (5-25%) of patients has recurrent disease within 5 years. There is need to identify these high-risk patients as they might benefit from additional treatment. Stroma-tissue surrounding the cancer cells plays an important role in the tumor behavior. The proportion of intra-tumor stroma was evaluated for the identification of high-risk patients. In addition, protein expression of markers involved in pathways related to stroma production and epithelial-to-mesenchymal transition (EMT) was analyzed: beta-catenin, TGF-beta-R2 and SMAD4.In a retrospective study of 135 patients with stage I-II colon cancer, the amount of stroma was estimated on routine haematoxylin-eosin stained histological sections. Sections were also immunohistochemically stained for beta-catenin, TGF-beta-R2 and SMAD4.Of 135 analyzed patients 34 (25.2%) showed a high proportion of stroma (stroma-high) and 101 (74.8%) a low proportion (stroma-low). Significant differences in overall-survival and disease-free-survival were observed between the two groups, with stroma-high patients showing poor survival (OS p<0.001, HZ 2.73, CI 1.73-4.30; DFS p<0.001, HZ 2.43, CI 1.55-3.82). A high-risk group was identified with stroma-high and SMAD4 loss (OS p=0.008, HZ 7.98, CI 4.12-15.44, DFS p=0.005, HZ 6.57, CI 3.43-12.56); 12 of 14 (85.7%) patients died within 3 years. In a logistic-regression analysis a high proportion of stroma and SMAD4 loss were strongly related (HZ 5.42, CI 2.13-13.82, p<0.001).Conventional haematoxylin-eosin stained tumor slides contain more prognostic information than previously fathomed. This can be unleashed by assessing the tumor-stroma ratio. The combination of analyzing the tumor-stroma ratio and staining for SMAD4 results in an independent parameter for confident prediction of clinical outcome.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
SMAD4 dec exp colorectal cancer not applicable N/A Clinical Study Prognostic In clinical and meta-analyses, decreased expression of Smad4 was correlated with poor prognosis in colorectal cancer (PMID: 25749173, PMID: 19478385, PMID: 25681512, PMID: 26861460). 25749173 19478385 26861460 25681512