Clinical outcome and pathological features associated with NRAS mutation in cutaneous melanoma

Pigment Cell Melanoma Res. 2011 Aug;24(4):666-72. doi: 10.1111/j.1755-148X.2011.00873.x. Epub 2011 Jun 22.


The effect of NRAS mutations on the pathological features and clinical outcomes in patients with cutaneous melanoma was compared with that of tumors containing BRAF(V600E) mutations and tumors wild type for both (WT). Clinical outcome data were obtained from a prospective cohort of 249 patients. Mutations involving NRAS and BRAF(V600E) were detected by PCR and were sequence verified. Cox proportional hazards regression was performed to relate NRAS and BRAF mutations to clinical outcome. Seventy-five percentage of NRAS mutations occurred in tumors >1 mm thick (BRAF(V600E) 40%, WT 34%); 75% of NRAS mutations had >1 mitosis/mm(2) (BRAF(V600E) 40%, WT 55%). When compared to WT, multivariate analysis of melanoma-specific survival (MSS) identified NRAS mutations as an adverse prognostic factor [hazard ratio (HR) 2.96; P = 0.04] but not BRAF(V600E) mutations (HR 1.73; P = 0.23). NRAS mutations were associated with thicker tumors and higher rates of mitosis when compared to BRAF(V600E) and WT melanoma and independently of this, with shorter MSS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Proliferation
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Melanoma / complications
  • Melanoma / genetics*
  • Melanoma / pathology*
  • Melanoma / therapy
  • Middle Aged
  • Mitosis
  • Mutation / genetics*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Skin Neoplasms / complications
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / therapy
  • Sunburn / complications
  • Treatment Outcome
  • Young Adult
  • ras Proteins / genetics*


  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • ras Proteins