Linked Life Data

17388789

Source:http://linkedlifedata.com/resource/pubmed/id/17388789

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-4-11
pubmed:abstractText
The extracellular-regulated kinase (ERK) signaling pathway plays important roles in regulating the malignant potential of cancer cells in vitro. However, the effect of ERK signaling on the prognosis of human tumors is not clearly understood. The present study examined the expression of phosphorylated ERK1/2 (p-ERK1/2) as a hallmark of ERK activation, in relation to KRAS and BRAF mutations, in 63 endometrial cancer specimens with endometrioid-subtype, in order to clarify the prognostic value of p-ERK1/2 expression. Immmunohistochemical analysis revealed that 40 tumors (63%) expressed p-ERK1/2, with varying levels of expression. Total ERK1/2 expression was also evaluated in a subset of tumors; most cases expressed ERK1/2 constitutively but no correlation was observed with p-ERK expression, indicating that p-ERK1/2 staining was not due to ERK overexpression but to hyperactivation of ERK1/2. There was no statistically significant correlation between p-ERK1/2 expression and clinicopathological features, including patient age, International Federation of Gynecology and Obstetrics stage, pathological grade, myometrial invasion and lymph node metastasis. Sequencing analysis indicated that 23% of patients had a mutation in exon 1 of KRAS, whereas none of the patients had a mutation in exons 11 or 15 of BRAF, which are reportedly hot spots for mutation in many tumor types. There was no significant correlation between KRAS or BRAF status and p-ERK1/2 expression. Unexpectedly, patients with low p-ERK1/2 expression had significantly lower relapse-free survival (P = 0.041) and overall survival (P = 0.020). Multivariate Cox regression analysis indicated that p-ERK1/2 expression was an independent prognostic indicator for overall survival (P = 0.047). These findings suggest that ERK activation occurs in a KRAS- and BRAF-independent manner in endometrial cancer, and is associated with favorable prognosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1347-9032
pubmed:author
pubmed:issnType
Print
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
652-8
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17388789-Adult, pubmed-meshheading:17388789-Aged, pubmed-meshheading:17388789-Blotting, Western, pubmed-meshheading:17388789-Butadienes, pubmed-meshheading:17388789-Cell Line, pubmed-meshheading:17388789-Endometrial Neoplasms, pubmed-meshheading:17388789-Enzyme Activation, pubmed-meshheading:17388789-Enzyme Inhibitors, pubmed-meshheading:17388789-Epidermal Growth Factor, pubmed-meshheading:17388789-Female, pubmed-meshheading:17388789-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17388789-Genes, ras, pubmed-meshheading:17388789-Humans, pubmed-meshheading:17388789-Immunohistochemistry, pubmed-meshheading:17388789-Kaplan-Meier Estimate, pubmed-meshheading:17388789-Middle Aged, pubmed-meshheading:17388789-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:17388789-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:17388789-Mutation, pubmed-meshheading:17388789-Nitriles, pubmed-meshheading:17388789-Phosphorylation, pubmed-meshheading:17388789-Prognosis, pubmed-meshheading:17388789-Proportional Hazards Models, pubmed-meshheading:17388789-Proto-Oncogene Proteins B-raf, pubmed-meshheading:17388789-RNA, Messenger, pubmed-meshheading:17388789-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2007
pubmed:articleTitle
Activation of ERK1/2 occurs independently of KRAS or BRAF status in endometrial cancer and is associated with favorable prognosis.
pubmed:affiliation
Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kanazawa University, 13-1, Takaramachi, Kanazawa, Ishikawa 920-8641, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't