Detection of Epidermal Growth-Factor Receptor and C-Erbb-2 Gene Amplification in Transitional-Cell Bladder-Carcinoma Using the Differential PCR Technique

Abstract

Abstract. Amplification of genes associated with cell control and differentiation is found in many human tumours and its detection may have important value in predicting tumour progression. In this study we examined 72 DNA samples extracted from paraffin-fixed formalin-embedded transitional cell carcinomas with a novel differential PCR technique that can detect variations in gene dosage using small amounts of tumour DNA. We have observed that this technique under certain conditions has many advantages over traditional gene analysis techniques. Our study revealed EGF-r and c-erbB-2 gene amplification in 2/72 (3%) and 11/72 (15%) bladder carcinomas, respectively. EGF-r gene was amplified in 2/24 (8%) grade III carcinomas while c-erbB-2 was amplified in 2/25 (8%) and 9/24 (37.5%) grade II and grade III carcinomas, respectively. All cases with EGF-r and c-erbB-2 gene increased copy number were classified as invasive on the basis of muscularis propia invasion. The association between c-erbB-2 amplification and tumour grade as well as stage of the carcinomas was statistically significant indicating direct linkage to bladder carcinoma progression, while the relationship between EGF-r gene amplification and the above mentioned parameters did not reach significance.