Prognostic Impact Of P53, EGFR And HER2/Neu Proteins On Renal Cell Carcinoma

摘要

The expression of p53, HER2eu and EGFR in renal cell carcinoma was studied using immunohistochemical methods in paraffin-embedded nephrectomy specimens from 40 patients. Expression of p53, EGFR and HER2eu was observed in 22 (55%), 33 (82.5%) and 10 (25%) patients respectively. In the Cox regression analysis overall expression of p53 was not statistically significant with a p value of 0.5 for total expression, 0.6 for weak expression and 0.2 for strong p53 expression. The HER2 positivity was also not statistically significant with a p value of 0.2 and a hazard ratio of 0.4. Similar results were obtained for EGFR overexpression with a p value of 0.591 for overall positivity, 0.3 for weak staining and 0.56 for strong staining. Our results indicate that p53, EGFR and HER2eu proteins may play a role in determining the prognosis in RCC. However the results were insignificant and a greater patient cohort is required before any true conclusions can be made. Introduction Renal cell carcinoma (RCC) is the most common malignancy of the adult kidney. The clinical outcome of RCC is generally determined by clinical stage and histologic grade and can vary considerably (Skinner at., 1971). However clinical staging is not entirely accurate in predicting the prognosis. Therefore several studies have focused on evaluating additional indicators of biologic aggressiveness of RCC. A variety of proteins and carbohydrates have been investigated for their use as prognostic tumour markers.The tumour suppressor gene p53 encodes a nuclear phosphoprotein involved in detecting DNA damage and allowing DNA repair or apoptosis: As a result of DNA damage cellular progression from G1 to S phase is halted to allow time for repair to occur. In this way mutations are corrected and prevented from accumulating in the cell. Mutations in the p53 gene are one of the most common genetic abnormalities in malignancies. It is generally accepted that p53 hyperexpression is the consequence of an increase in the half-life of the non-functional protein which is usually related to mutation of the gene and is easily detectable by immunohistochemistry. The HER-2eu oncogene (also named c-erbB2) encodes a 185kDa transmembrane glycoprotein with tyrosine kinase activity and extended homology in structure and sequences to the EGFR (Coussens et al., 1985). It can heterodimerise with the EGFR to generate a more efficient mitogenic signal than either the EGFR itself or the HER2eu homodimer (Dougall et al., 1994). HER2eu amplification and overexpression has been associated with a number of malignancies including breast and ovarian tumours (Slamon et al., 1989), transitional cell carcinoma (Chow et al., 1997), colon carcinoma (Brossart 1998), prostatic adenocarcinoma (Kallakury et al., 1998), cervical carcinoma (Ndubisi et al., 1997), gastric carcinoma and non-small cell lung carcinoma (Yoshino et al., 1994). The Epidermal growth factor receptor (EGFR) is a 170 kilodalton transmembrane cell-surface receptor which has tyrosine kinase activity. It is overexpressed in a third of all epithelial cancers and is frequently associated with a poor prognosis (Lieberman et al., 1985, Ozanne et al., 1986, Neal et al., 1990). Blockage of EGFR using monoclonal antibodies has been shown to promote inhibition of the malignant phenotype (Rubin Grandis et al., 1997) The purpose of this retrospective study was to investigate expression of p53, HER2eu and EGFR in 40 patients with RCC and correlate their expression with prognosis Materials And Methods Patients and Tumour CharacteristicsThis study used data from 40 patients (25 men, 15 women) who underwent surgery for RCC between 1990 and 2000 (table 1). The mean age of the patients was 65.2 years (range 25 to 85). The follow up period was at least 4 years. The main clinical and pathological characteristics included in our study are shown in table 1. Tissue samples from 40 patients were analyzed. Three of the patients had papillary RCC and the rem