Immunohistochemistry as a potential tool for routine detection of the NRAS Q61R mutation in patients with metastatic melanoma

J Am Acad Dermatol. 2015 May;72(5):786-93. doi: 10.1016/j.jaad.2015.01.012. Epub 2015 Feb 7.


Background: It can be useful to assess the NRAS mutation status in patients with metastatic melanoma because NRAS-activating mutations confer resistance to RAF inhibitors, and NRAS-mutated patients appear to be sensitive to mitogen-activated protein kinase (MEK) inhibitors.

Objective: We aimed to assess the diagnostic accuracy of an immunohistochemistry (IHC) approach using a novel anti-NRAS (Q61R) monoclonal antibody on formalin-fixed paraffin-embedded tissue samples from patients with metastatic melanoma.

Methods: We conducted a retrospective multicenter cohort study on 170 patients with metastatic melanoma. The automated IHC assay was performed using the SP174 clone, and compared with results of the molecular testing.

Results: Evaluation of a test cohort with knowledge of the mutation status established a specific IHC pattern for the mutation. In the independent blinded analysis of the remaining cases, the anti-NRAS (Q61R) antibody accurately identified all NRAS Q61R-mutated tumors, and demonstrated 100% sensitivity and specificity.

Limitations: Limitations include retrospective design and lack of multicenter interobserver reproducibility.

Conclusion: The NRAS (Q61R) IHC assay is reliable and specific for the evaluation of the Q61R mutation status in metastatic melanoma and may be an alternative to molecular biology in evaluation of metastatic melanoma in routine practice.

Keywords: NRAS; Q61R mutation; SP174 clone; immunohistochemistry; metastatic melanoma; molecular biology.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal
  • Cohort Studies
  • Female
  • GTP Phosphohydrolases / genetics*
  • GTP Phosphohydrolases / immunology
  • Humans
  • Immunohistochemistry* / methods
  • Male
  • Melanoma / genetics*
  • Membrane Proteins / genetics*
  • Membrane Proteins / immunology
  • Middle Aged
  • Mutation*
  • Neoplasm Metastasis / genetics*
  • Retrospective Studies
  • Skin Neoplasms


  • Antibodies, Monoclonal
  • Membrane Proteins
  • GTP Phosphohydrolases
  • NRAS protein, human

Supplementary concepts

  • Melanoma, Cutaneous Malignant