Molecular markers

RAS Q61R IHC


Editorial Board Member: Ruta Gupta, M.D.
Deputy Editor-in-Chief: Patricia Tsang, M.D., M.B.A.
Leila Moayed-Alaei, M.D.
Andrew J. Colebatch, M.B.B.S., Ph.D.

Last author update: 30 May 2023
Last staff update: 30 May 2023

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PubMed Search: RAS Q61R

Leila Moayed-Alaei, M.D.
Andrew J. Colebatch, M.B.B.S., Ph.D.
Page views in 2024 to date: 459
Cite this page: Moayed-Alaei L, Colebatch A. RAS Q61R IHC. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsNRAS.html. Accessed May 19th, 2024.
Definition / general
Essential features
  • RAS Q61R immunohistochemistry (IHC) is mutation specific, with immunoreactivity against NRAS Q61R, KRAS Q61R and HRAS Q61R
  • Strong and diffuse cytoplasmic or membranous staining of RAS Q61R is interpreted as positive
Terminology
  • Neuroblastoma RAS viral oncogene homolog
Pathophysiology
  • NRAS is a proto-oncogene located on chromosome 1p13.2
  • NRAS encodes a protein with GTPase activity (Clin Cancer Res 2014;20:4186)
  • In its normal state, NRAS protein transmits proliferation signals (i.e., cytokines, hormones and growth factors in to the cell), which are critical for proliferation, differentiation and survival (My Cancer Genome: NRAS [Accessed 31 January 2023], Nucleic Acids Res 2019;47:D506)
  • Downstream signaling pathways triggered by NRAS include RAF-MEK-ERK (MAP) kinases and PI3-AKT kinases (Proc Natl Acad Sci U S A 2014;111:4179)
  • Point mutations in hotspot codons within exon 2 [codons 12 and 13] and exon 3 [codon 61] lead to aberrant activation of the RAS pathway; this mutation disrupts GTPase activity and keeps RAS in the activated state (GTP bound) (Proc Natl Acad Sci U S A 2014;111:4179)
  • Somatic mutations of NRAS in cancer commonly occur at codon 61, including Q61R; similar mutations occur in HRAS and KRAS, at lower relative frequencies
  • RAS Q61R mutation specific antibody (SP174) was initially designed to detect NRAS Q61R mutations; however, it is also reactive against KRAS and HRAS Q61R mutations due to homology (Histopathology 2021;79:650)
  • Anti-RAS Q61R antibody cannot distinguish between NRAS Q61R, KRAS Q61R and HRAS Q61R mutations due to sequence homology at these loci
Diagrams / tables

Images hosted on other servers:
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Mechanism of NRAS activation

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NRAS pathway

Clinical features
Interpretation
Uses by pathologists
Microscopic (histologic) images

Contributed by Leila Moayed-Alaei, M.D.
NRAS positive melanoma

NRAS positive melanoma

NRAS positive melanocytic lesion NRAS positive melanocytic lesion

NRAS positive melanocytic lesion


NRAS positive salivary duct carcinoma NRAS positive salivary duct carcinoma NRAS positive salivary duct carcinoma NRAS positive salivary duct carcinoma

NRAS positive salivary duct carcinoma

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Positive staining - normal
  • RAS Q61R staining is not seen in normal human tissue, as it results from a gain of function oncogenic mutation
Positive staining - disease
Sample pathology report
  • Skin, excision:
    • Melanoma (see comment)
    • Comment: Histologic section of skin to subcutis demonstrates melanoma. Immunohistochemistry shows moderate cytoplasmic and membranous staining for RAS Q61R and is negative for BRAF V600E.
Board review style question #1

Which of the following statements is true regarding RAS Q61R?

  1. NRAS gene encodes for a nuclear transcription factor that promotes cell growth
  2. Positive staining for RAS Q61R can be found in lesions with either NRAS Q61R, KRAS Q61R or HRAS Q61R mutations
  3. Positive staining for RAS Q61R is specific to NRAS Q61R mutation
  4. RAF is one of the upstream pathways that trigger NRAS
Board review style answer #1
B. Positive staining for RAS Q61R can be found in lesions with either NRAS Q61R, KRAS Q61R or HRAS Q61R mutation.

Comment Here

Reference: NRAS
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