J Korean Assoc Oral Maxillofac Surg.  2011 Oct;37(5):396-402.

Epidermal growth factor receptor overexpression and K-ras mutation detection in the oral squamous cell carcinoma

• Moon BC
• Han SJ
• Jeong D
• Kim KW

Abstract

INTRODUCTION
Epidermal growth factor is a single-chain polypeptide consisting of 53 amino acids with potent mitogenic activity that stimulates the proliferation of a range of normal and neoplastic cells through an interaction with its specific receptor (epidermal growth factor receptor, EGFR). This interaction plays a key role in tumor progression including the induction of tumor cell proliferation. An increased EGFR copy number have been associated with a favorable response to EGFR tyrosine kinase inhibitors therapy. In contrast, K-ras mutations tend to predict a poor response to such therapy. The aim of this study was to determine the correlation between the clinicopathological factors and the up-regulation of EGFR expression and Kras mutations in oral squamous cell carcinoma.
MATERIALS AND METHODS
This study examined the immunohistochemical staining of EGFR, K-ras mutation detection with peptide nucleic acid (PNA)-based real-time polymerase chain reaction (PCR) clamping in 20 specimens from 20 patients with oral squamous cell carcinoma.
RESULTS
1. In the immunohistochemical study of poorly differentiated and invasive oral squamous cell carcinoma, a high level of EGFR staining was observed. The correlation between immunohistochemical EGFR expression and histological differentiation, as well as the tumor size of the specimens was significant (Pearson correlation analysis, significance [r] >0.5, P<0.05). 2. In PNA-based real-time PCR clamping analysis, a K-ras mutation was not detected in all specimens.
CONCLUSION
These findings suggest that the up-regulation of the EGFR may play a role in the progression and invasion of oral squamous cell carcinoma that is, independent of a K-ras mutation.

Keyword

Squamous cell carcinoma; Epidermal growth factor receptor; ras Proteins

MeSH Terms

Amino Acids
Carcinoma, Squamous Cell
Cell Proliferation
Coat Protein Complex I
Constriction
Epidermal Growth Factor
Humans
Protein-Tyrosine Kinases
ras Proteins
Real-Time Polymerase Chain Reaction
Receptor, Epidermal Growth Factor
Up-Regulation
Amino Acids
Coat Protein Complex I
Epidermal Growth Factor
Protein-Tyrosine Kinases
Receptor, Epidermal Growth Factor
ras Proteins

Figure

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  Fig. 1. Real-time PCR cyclining condition. Byeong-Chool Moon et al: Epidermal growth factor receptor overexpression and K-ras mutation detection in the oral squamous cell carcinoma. J Korean Assoc Oral Maxillofac Surg 2011

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  Fig. 2. The PNA probe which is complementary to the wild type K-ras binds to the K-ras gene completely and the PCR is inhibited, while on mutant K-ras gene, the PNA probe binds to the mutan K-ras gene imcompletely and PCR is not inhibited resulting in amplicon. Byeong-Chool Moon et al: Epidermal growth factor receptor overexpression and K-ras mutation detection in the oral squamous cell carcinoma. J Korean Assoc Oral Maxillofac Surg 2011

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  Fig. 3. Negative immunohistochemical staining for EGFR of well differentiated oral squamous cell carcinoma (anti-EGFR Immunoperoxidase, ×100). EGFR, epidermal growth factor receptor. Byeong-Chool Moon et al: Epidermal growth factor receptor overexpression and K-ras mutation detection in the oral squamous cell carcinoma. J Korean Assoc Oral Maxillofac Surg 2011

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  Fig. 4. Mild immunohistochemical staining for EGFR of moderate differentiated oral squamous cell carcinoma (anti-EGFR Immunoperoxidase. ×100). EGFR, epidermal growth factor receptor. Byeong-Chool Moon et al: Epidermal growth factor receptor overexpression and K-ras mutation detection in the oral squamous cell carcinoma. J Korean Assoc Oral Maxillofac Surg 2011

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  Fig. 5. Moderate immunohistochemical staining for EGFR of poor differentiated oral squamous cell carcinoma (anti-EGFR Immunoperoxidase, ×100). EGFR, epidermal growth factor receptor. Byeong-Chool Moon et al: Epidermal growth factor receptor overexpression and K-ras mutation detection in the oral squamous cell carcinoma. J Korean Assoc Oral Maxillofac Surg 2011

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  Fig. 6. Severe immunohistochemical staining for EGFR of poor differentiated and invasive oral squamous cell carcinoma (anti-EGFR Immunoperoxidase, ×100). EGFR, epidermal growth factor receptor. Byeong-Chool Moon et al: Epidermal growth factor receptor overexpression and K-ras mutation detection in the oral squamous cell carcinoma. J Korean Assoc Oral Maxillofac Surg 2011

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  Fig. 7. K-ras mutation detection with PNA-based real-time PCR clamping. Byeong-Chool Moon et al: Epidermal growth factor receptor overexpression and K-ras mutation detection in the oral squamous cell carcinoma. J Korean Assoc Oral Maxillofac Surg 2011

Reference

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