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Molecular and immunohistochemical study of class I growth factor receptors in squamous cell lung carcinomas
V Gorgoulis1, P P Sfikakis, A Karameris
1First Department of Propedeutic Medicine, University of Athens Medical School, Greece.
Abstract:
The class I growth factor receptor family includes epidermal growth factor receptor, i.e. c-erbB-1, c-erbB-2 and c-erbB-3 molecules. These receptors have a significant sequence homology and play an important role in cell growth and differentiation. To further investigate their implication in squamous cell lung carcinomas (SqCLCs), we studied the protein expression by immunohistochemistry and examined for possible gene amplification by a novel semi-quantitative differential polymerase chain reaction (DPCR) technique. Expression of c-erbB-1, c-erbB-2 and c-erbB-3 was present in 65%, 28% and 10% respectively, of 40 SqCLCs cases. Seven of the 11 cases that expressed c-erbB-2, as well as all 4 c-erbB-3 expressing cases, also stained with the anti-c-erbB-1 mAb. Expression of c-erbB-1, but not of c-erbB-2 or c-erbB-3, correlated with the grade of tumor differentiation (100%, 64% and 36% positive cases of well, moderately and poorly differentiated cases respectively, p < 0.003). In addition, c-erbB-1 expression correlated with the presence of regional lymph node metastases within the moderately differentiated group. The c-erbB-1 gene was amplified in 11/40 (28%) cases, all of which overexpressed c-erbB-1 protein, while c-erbB-2 gene amplification was detected in only one case. There was no c-erbB-3 gene amplification in any of the 40 SqCLCs cases. These findings suggest that c-erbB-1, c-erbB-2 and c-erbB-3 receptors do not have a common role and are of different physiological importance, at least at the stage of clinically overt tumor in human SqCLCs.
Insights
Epidermal growth factor receptor (EGFR) family members c-erbB-1, c-erbB-2, and c-erbB-3 were studied in squamous cell lung carcinomas (SqCLCs). c-erbB-1 expression correlated with tumor differentiation and metastasis, unlike c-erbB-2 and c-erbB-3.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The class I growth factor receptor family, including epidermal growth factor receptor (EGFR) family members c-erbB-1, c-erbB-2, and c-erbB-3, are crucial for cell growth and differentiation.
- Understanding the roles of these receptors in squamous cell lung carcinomas (SqCLCs) is vital for targeted therapies.
Purpose of the Study:
- To investigate the protein expression and gene amplification of c-erbB-1, c-erbB-2, and c-erbB-3 in SqCLCs.
- To determine the correlation between the expression of these receptors and clinicopathological features of SqCLCs.
Main Methods:
- Immunohistochemistry was used to assess protein expression of c-erbB-1, c-erbB-2, and c-erbB-3 in 40 SqCLC samples.
- A novel semi-quantitative differential polymerase chain reaction (DPCR) technique was employed to detect gene amplification of c-erbB-1, c-erbB-2, and c-erbB-3.
Main Results:
- Protein expression was observed in 65% for c-erbB-1, 28% for c-erbB-2, and 10% for c-erbB-3.
- c-erbB-1 expression correlated significantly with tumor differentiation (p < 0.003) and lymph node metastasis in moderately differentiated tumors.
- Gene amplification was found in 28% of cases for c-erbB-1 and one case for c-erbB-2, with no amplification for c-erbB-3.
Conclusions:
- The c-erbB-1, c-erbB-2, and c-erbB-3 receptors exhibit distinct roles and physiological importance in SqCLCs.
- c-erbB-1 appears to be a significant factor in SqCLC progression, correlating with differentiation and metastasis.