ArticleWorld journal of surgical oncology2012
ERK/pERK expression and B-raf mutations in colon adenocarcinomas: correlation with clinicopathological characteristics.
Article in World journal of surgical oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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21 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Signal transduction pathway mutations in gastrointestinal (GI) cancers: a systematic review and meta-analysis.Scientific reports · 2020Pooled it
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- Seasonal expression of extracellular signal regulated kinases in the colon of wild ground squirrels (Spermophilus dauricus).Molecular biology reports · 2022Article
- Concomitant Mutations G12D and G13D on the Exon 2 of the KRAS Gene: Two Cases of Women with Colon Adenocarcinoma.Diagnostics (Basel, Switzerland) · 2021Article
- Mutational profile of skin lesions in hepatocellular carcinoma patients under tyrosine kinase inhibition: a repercussion of a wide-spectrum activity.Oncotarget · 2021Article
- Decreased concentrations of intracellular signaling proteins in colon cancer patients with BRAF mutations.Scientific reports · 2020Article
- Integrin α1 promotes tumorigenicity and progressive capacity of colorectal cancer.International journal of biological sciences · 2020Article
- Identifying the ErbB/MAPK Signaling Cascade as a Therapeutic Target in Canine Bladder Cancer.Molecular pharmacology · 2019Article
- Relationships amongWorld journal of gastroenterology · 2019Article
- Linking FOXO3, NCOA3, and TCF7L2 to Ras pathway phenotypes through a genome-wide forward genetic screen in human colorectal cancer cells.Genome medicine · 2018Article
- A transcriptional MAPK Pathway Activity Score (MPAS) is a clinically relevant biomarker in multiple cancer types.NPJ precision oncology · 2018Article
- Zinc-finger protein 545 is inactivated due to promoter methylation and functions as a tumor suppressor through the Wnt/β-catenin, PI3K/AKT and MAPK/ERK signaling pathways in colorectal cancer.International journal of oncology · 2017Article
- Expression of phosphorylated extracellular signal-regulated kinase at the invasive front of hepatic colorectal metastasis.Oncology letters · 2015Article
- Clinicopathologic Significance of BRAF Mutation and Extracellular Signal Regulated Kinase 1/2 Expression in Patients With a Colorectal Adenocarcinoma.Annals of coloproctology · 2015Article
- Article
- Overexpression of Raf-1 and ERK1/2 in sacral chordoma and association with tumor recurrence.International journal of clinical and experimental pathology · 2015Article
- PBX3 promotes migration and invasion of colorectal cancer cells via activation of MAPK/ERK signaling pathway.World journal of gastroenterology · 2014Article
- Extracellular signal-regulated kinase (ERK) expression and activation in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- SATB1 expression is associated with biologic behavior in colorectal carcinoma in vitro and in vivo.PloS one · 2013Article
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11 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundColorectal (CRC) carcinogenesis through various morphological stages has been linked to several genetic and epigenetic changes. The Raf/MEK/ERK (MAPK) signal transduction cascade is an important mediator of a number of cellular fates.
methodsIn this study, we investigated the presence of B-raf and K-ras mutations in 94 consecutive cases of primary colon adenocarcinoma in correlation with the immunohistochemical expression of total and activated ERK and the expression of mismatch repair proteins (MMR) hMLH1 and hMSH2 as well as their correlations with standard clinicopathological parameters.
resultsThe immunostaining pattern for total and activated ERK was nuclear and cytoplasmic. hMLH1 and hMSH2 proteins were preserved in 45/63 (71.43%) cases and 35/53 (66.04%) cases respectively. Total ERK nuclear expression, was positively correlated with tumor stage (p = 0.049), whereas nuclear pERK expression was positively correlated with histological grade (p = 0.0113) and tumor stage (p = 0.0952), although the latter relationship was of marginal significance. DNA sequencing showed that 12 samples (12.7%) had a mutation in B-RAF Exon 15 and none in Exon 11, whereas 22 (23.4%) had a K-ras mutation. Disruption of the MAP kinase pathway-either through K-ras or B-raf mutation-was detected in 37% of all the examined cases, although the overexpression of total and activated ERK1/2 was not correlated with the mutational status of K-ras or B-raf genes. Finally, the preservation of hMLH1 or hMSH2 immunoexpression was not correlated with the presence of B-raf and/or K-ras mutations.
conclusionsIn this study, we present evidence that ERK activation occurs in a K-ras or B-raf -independent manner in the majority of primary colon cancer cases. Moreover, B-raf mutations are not associated with mismatch-repair deficiency through loss of hMLH1 or hMSH2 expression. Activated ERK could possibly be implicated in tumor invasiveness as well as in the acquisition of a more aggressive phenotype.
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