Reference Detail

Ref Type

Journal Article

PMID

(25681512)

Authors

Kozak MM, von Eyben R, Pai J, Vossler SR, Limaye M, Jayachandran P, Anderson EM, Shaffer JL, Longacre T, Pai RK, Koong AC, Chang DT

Title

Smad4 inactivation predicts for worse prognosis and response to fluorouracil-based treatment in colorectal cancer.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of clinical pathology	68	5	2015 May	341-5	J Clin Pathol

URL

Abstract Text

To determine whether expression of Smad4, a tumour suppressor found to be absent in 10% of colorectal cancer (CRC), is associated with outcomes in patients with CRC.Tumour samples from 241 consecutive patients with CRC who underwent upfront colon resection between 2005 and 2009 were obtained. Triplicate tissue cores from resected primary colon tumours and matched normal controls were used to construct the tissue microarrays (TMAs). We examined the expression of Smad4 using immunohistochemistry. Clinicopathological records were obtained for all patients. TMAs were reviewed by two pathologists and scored as either 'positive' or 'negative' for nuclear staining. In total, 21 of 241 tumours (8.6%) were Smad4 negative.Loss of Smad4 expression correlated with significantly worse overall survival (OS) (p=0.011) and disease-free survival (DFS) (p=0.024). Patients with loss of Smad4 expression had a median OS of 31 months compared with 89 months positive Smad4 expression. Loss of Smad4 remained significant on multivariate analysis for OS (p=0.0097). In patients with node-positive disease, loss of Smad4 predicts for worse DFS (p=0.012). In patients with metastatic and recurrent disease, Smad4 loss predicts for worse OS (p=0.012). Of the patients that received capecitabine over the course of their treatment, those with Smad4 loss (n=13) had significantly worse DFS (p=0.003) and OS (p=0.0007).Loss of Smad4 expression is associated with worse DFS and OS in multiple subsets of patients with CRC. Further studies are required to validate our findings and ascertain the role of Smad4 status in the management of this disease.

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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