Expression of epidermal growth factor receptor in bladder cancer as related to established prognostic factors, oncoprotein (c-erbB-2, p53) expression and long-term prognosis

Abstract

Summary The expression of epidermal growth factor receptor (EGFR) was studied immunohistochemically in 234 cases of transitional cell bladder cancer. EGFR was overexpressed in 35% of cases and distinct nuclear localisation of EGFR positivity was found in 31% of the tumours. Overexpression was related to invasive growth, grade 2-3 histology, non-papillary type, DNA aneuploidy and high proliferation rate of cancer cells. The expressions of p53 and EGFR were interrelated, while expression of c-erbB-2 was independent of EGFR expression. Progression of superficial tumours, recurrence-free survival and survival were independently related to overexpression of EGFR in multivariate analysis. T category, S-phase fraction and non-papillary type included all the available prognostic information when the entire cohort was analysed by multivariate methods. The results show that overexpression of EGFR is related to several malignant features and prognosis in superficial bladder cancer. Moreover, the results suggest that overexpression of EGFR is usually a late event in bladder cancer development related to genetic instability rather than an early event in malignant transformation. Further studies are still needed to establish whether the direct measurement of cell proliferation or analysis of growth factor receptors and other oncoproteins gives more accurate prognostic information in bladder cancer.

Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival

“…Nuclear expression of EGFR was further detected in other cell types and tissues, such as placentas, thyroids and immortalized epithelial cells of ovary and kidney origins (Cao et al, 1995;Lin et al, 2001;Marti et al, 2001;Lo et al, 2005a). High levels of EGFR was also found in the nuclei of many tumours, including those of skin, breast, bladder, cervix, adrenocorticord, thyroid and oral cavity (Kamio et al, 1990;Lipponen and Eskelinen, 1994;Lin et al, 2001;Marti et al, 2001;Lo et al, 2005a, c;Psyrri et al, 2005). In addition, EGFR has been shown to localize in the inner nuclear membrane (Cao et al, 1995;Klein et al, 2004).…”

The Prolactin Receptor Transactivation Domain Is Associated with Steroid Hormone Receptor Expression and Malignant Progression of Breast Cancer

“…For instance, initial studies found EGFR in the nuclei of cells from various tissues, including thyroid cells, immortalized renal and ovarian epithelial cells, and primary tumors of the bladder and thyroid. 38,39 In subsequent reports, nuclear EGFR, but not cytoplasmic EGFR, positively correlated with tumor size and lymph node metastasis and negatively correlated with survival in breast cancer. 23 A microarray study demonstrated that several genes, including COX2, were activated by EGFR, but not by nuclear localizationedefective EGFR.…”

Matrix metalloproteinase-1 is induced by epidermal growth factor in human bladder tumour cell lines and is detectable in urine of patients with bladder tumours

“…The elevation of serum levels of either MMP2 or MMP3, or both, were also shown to be possible predictors of recurrence in patients with advanced urothelial carcinoma after resection (Gohji et al, 1996b). In contrast Grignon et al (1996) suggests that there is a strong correlation between high levels of TIMP2 immunostaining and poor outcome in patients with invasive bladder cancer.Growth factors and their receptors are important in tumour development and progression and several studies have shown that the presence of epidermal growth factor receptor (EGFR) in bladder cancer is associated with high tumour stage and grade and is a strong independent predictor of tumour progression and poor long-term survival (Lipponen and Eskelinen, 1994;Mellon et al, 1995). Levels of epidermal growth factor (EGF) are known to be high in urine with a mean value of 80 ng ml-' (Fisher and 215 …”

“…Growth factors and their receptors are important in tumour development and progression and several studies have shown that the presence of epidermal growth factor receptor (EGFR) in bladder cancer is associated with high tumour stage and grade and is a strong independent predictor of tumour progression and poor long-term survival (Lipponen and Eskelinen, 1994;Mellon et al, 1995). Levels of epidermal growth factor (EGF) are known to be high in urine with a mean value of 80 ng ml-' (Fisher and Lakshmanan, 1990), but are lower in patients with bladder tumours and rise again after surgery (Fuse et al, 1992).…”