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Related Experiment Videos

ras mutations and expression in head and neck squamous cell carcinomas

W G Yarbrough1, C Shores, D L Witsell

  • 1Division of Otolaryngology/Head & Neck Surgery, University of North Carolina School of Medicine, Chapel Hill.

The Laryngoscope
|November 1, 1994
PubMed
Summary

Mutational activation of ras genes is not common in head and neck squamous cell carcinomas (SCCs). However, altered expression of N-ras, particularly overexpression and changes in expression patterns during dysplasia, suggests a role in head and neck cancer development.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Ras proto-oncogenes are frequently altered in human tumors.
  • The specific roles of H-ras, K-ras, and N-ras mutations and protein (p21) expression in head and neck squamous cell carcinoma (SCC) development are not fully understood.

Purpose of the Study:

  • To investigate the frequency of ras gene mutations in head and neck SCC.
  • To analyze the expression patterns of H-ras, K-ras, and N-ras proteins in normal mucosa, dysplastic mucosa, and SCC of the head and neck.
  • To determine if ras protein expression correlates with tumor characteristics or stages of carcinogenesis.

Main Methods:

  • Analysis of codons 12, 13, and 61 of H-ras, K-ras, and N-ras for mutations in 51 head and neck SCC samples.
  • Immunocytochemistry (ICC) to assess the expression of p21H-ras, p21K-ras, and p21N-ras proteins.

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  • Correlation of protein expression with histological differentiation and TNM staging.

    • Main Results:

    • No mutations in H-ras, K-ras, or N-ras were detected in the analyzed codons of head and neck SCCs.
    • p21N-ras was expressed in normal basal layers, with reduced expression in mature cells; p21H-ras showed low expression in all layers; p21K-ras was not expressed in normal mucosa.
    • p21N-ras was overexpressed in 7/9 SCCs and showed altered expression patterns in dysplastic mucosa, present in all layers compared to normal mucosa.
    • p21H-ras and p21K-ras were expressed in a subset of SCCs, with no correlation to differentiation or staging.

    Conclusions:

    • Mutational activation of ras is not a significant event in the majority of head and neck SCCs.
    • Altered expression of N-ras, including overexpression and changes in expression patterns during dysplasia, suggests a potential role in the early stages of head and neck SCC development.
    • Loss of control over N-ras expression may be an early carcinogenic event in head and neck SCC.