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Lack of Cytoplasmic ERK Activation Is an Independent Adverse Prognostic Factor in Primary Cutaneous Melanoma
- Source :
- Journal of Investigative Dermatology. 128(11):2696-2704
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- The aim of this study was to estimate the impact on survival of NRAS and BRAF mutations and activation of Akt and extracellular signal-regulated kinase (ERK) in primary melanomas. A cohort of 57 primary cutaneous T1-2 melanoma tumors was analyzed. Mutation frequency for both genes was 61% (NRAS 26% and BRAF 39%). In a univariate analysis, shorter overall survival was associated with the presence of ulceration (P=0.001) and BRAF exon 15 mutations (P=0.005) as well as the absence of nuclear activation of Akt (P=0.022) and of cytoplasmic activation of ERK (P=0.003). Unexpectedly, ulceration was a significant adverse prognostic factor only in melanomas with BRAF mutations, whereas there was no effect of ulceration on overall survival in tumors with wild-type BRAF. A multivariate analysis showed that significant independent adverse survival prognostic markers were absence of cytoplasmic activation of ERK (P=0.007) and ulceration (P=0.008), whereas BRAF exon 15 mutation status showed a nonsignificant trend (P=0.066). The absence of cytoplasmic ERK activation in poor prognosis T1-2 melanomas may be associated with activation of some other uncharacterized pathway leading to tumor progression and adverse outcome. Immunohistochemical analysis of cytoplasmic phosphorylated ERK could be used as a prognostic marker in primary melanomas if confirmed in another data set.
- Subjects :
- Adult
Male
Proto-Oncogene Proteins B-raf
Neuroblastoma RAS viral oncogene homolog
MAPK/ERK pathway
Cytoplasm
Pathology
medicine.medical_specialty
Skin Neoplasms
Biopsy
Kaplan-Meier Estimate
Dermatology
Biochemistry
Cohort Studies
Biomarkers, Tumor
medicine
Humans
Melanoma
Protein kinase B
neoplasms
Molecular Biology
Aged
Aged, 80 and over
Mitogen-Activated Protein Kinase 1
business.industry
Cancer
Cell Biology
Middle Aged
Prognosis
medicine.disease
digestive system diseases
Oncogene Protein v-akt
Genes, ras
Tumor progression
Mutation
Cutaneous melanoma
Cancer research
Female
Skin cancer
business
Subjects
Details
- ISSN :
- 0022202X
- Volume :
- 128
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Journal of Investigative Dermatology
- Accession number :
- edsair.doi.dedup.....f7b75030d716aff40f66b904bfe5f7a8
- Full Text :
- https://doi.org/10.1038/jid.2008.134