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EGFR protein expression and gene copy number changes in conventional and papillary type renal cell carcinomas

초록/요약

The epidermal growth factor receptor (EGFR) is known to be involved in cell cycle progression, inhibition of apoptosis, angiogenesis, promotion of invasion/metastasis, and other tumor promoting activities. The inhibition of the EGFR is tried as one of the therapeutic modalities in a variety of human malignancies. To evaluate the role of EGFR in renal cell carcinomas (RCCs), the expression of EGFR protein and gene copy number change were studied in 135 conventional and 16 papillary RCCs. The TMA slides and clinicopathological features used in this study were obtained by the Urological Pathology Study Group of The Korean Society of Pathologists, which were diagnosed between 1995 and 1997. The membranous expression of EGFR on immunohistochemistry was scored as 0, 1+, 2+ or 3+, and 2+ and 3+ were accepted as a positive result. The gene copy number change of EGFR was detected by fluorescence in situ hybridization (FISH) technique using centromeric and EGFR probes. The EGFR expression was positive in 118 (87.4%) of 135 conventional RCCs, and 11 (68.8%) of 16 papillary RCCs. The strong expression of EGFR in conventional RCCs was associated with male gender, tumor size (≥4cm) and high T stages (T2 and T3) with statistical significance. No amplification of EGFR gene was detected in all examined RCCs. Trisomy and polysomy were found in 27 (25.7%) and 40 (38.1%) of 105 conventional RCCs. The trisomy and polysomy were correlated with EGFR protein expression, and high clinical T stage with statistical significances. Among 15 papillary RCCs, 13 tumors were showed trisomy (86.7%) and one polysomy (6.7%). There was no significant correlation of trisomy and polysomy in papillary RCCs with clinicopathological parameters. In conclusion, the strong expression of EGFR protein and gene copy number gains in RCCs may be used as a possible biologic predictor as well as in target therapy of an advanced renal cell carcinoma.

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Contents

Abstract---------------------------------------------i
I. Introduction--------------------------------------1
II. Material and Methods--------------------------3
III. Results-------------------------------------------9
IV. Discussion--------------------------------------13
V. References--------------------------------------17

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