Epidermal growth factor receptor expression in urinary bladder cancer

Abstract

Objective: To evaluate the expression pattern of epidermal growth factor receptor (EGFR) in urinary bladder cancer and its association with human epidermal growth factor receptor 2 (HER2), epidermal growth factor (EGF), interleukin-6 (IL-6), and high risk human papilloma virus (HPV) types 16 and 18.

Materials and methods: Thirty cases of urothelial carcinoma were analyzed. EGFR, HER2, EGF, and IL-6 expressions in the tissue were evaluated by immunohistochemical staining. For HPV, DNA from tissue samples was extracted and detection of HPV was done by PCR technique. Furthermore, evaluation of different intracellular molecules associated with EGFR signaling pathways was performed by the western blot method using lysates from various cells and tissues.

Results: In this study, the frequencies of immunopositivity for EGFR, HER2, EGF, and IL-6 were 23%, 60%, 47%, and 80%, respectively. No cases were positive for HPV-18, whereas HPV-16 was detected in 10% cases. Overall, expression of EGFR did not show any statistically significant association with the studied parameters. However, among male patients, a significant association was found only between EGFR and HER2.

Conclusions: Overexpression of EGFR and/or HER2, two important members of the same family of growth factor receptors, was observed in a considerable proportion of cases. Precise knowledge in this subject would be helpful to formulate a rational treatment strategy in patients with urinary bladder cancer.

Keywords: Epidermal growth factor receptor; human epidermal growth factor receptor 2; human papilloma virus; immunohistochemistry; urinary bladder carcinoma.

Figure 1

(a) Showing salient epidermal growth factor receptor (EGFR)-associated signaling pathways. EGFR: epidermal growth factor receptor, p-: phosphorylated, PKCα: protein kinase C α, PI3K: phosphatidylinositol 3-kinase, JAK1: janus kinase 1, STAT3: signal transducer and activator of transcription 3, ERK: extracellular signal-regulated kinase, MAPK: mitogen-activated protein kinase, MKK4: MAPK kinase 4, SAPK: stress activated protein kinase, JNK: c-jun amino-terminal kinase, Serine/threonine kinase (e.g., AKT, Raf). (b) Comparison between expressions of different EGFR-associated signaling molecules in various tissues and cell lines with reference to urinary bladder tissue. Lane 1: MCF-7 cells, Lane 2: Mouse mammary tissue, Lane 3: T47-D cells, Lane 4: LNCaP cells, Lane 5: PC-3 cells, Lane 6: TRAMP tumour tissue, Lane 7: Mouse urinary bladder tissue, Lane 8: SK-OV-3 cells, Lane 9: Mouse uterine tissue.

Figure 2

(a) Tumor tissue stained with hematoxylin and eosin. (b)Immunohistochemically negative tissue section. (c) Urinary bladder cancer tissue sections with overexpression of epidermal growth factor receptor. (d) Human epidermal growth factor receptor 2 (HER2). (e) Epidermal growth factor. and (f) interleukin-6.

Figure 3

PCR amplification of β-globin and human papilloma virus type 16 (HPV-16) gene showing amplimer of 268 bp and 217 bp. Lane 1: Molecular weight DNA standard, Lane 2: Positive control (Plasmid DNA), Lane 3: Positive control (HPV-16 positive cervical cancer), Lane 4: Negative control (C33a DNA), Lane 5: Negative control (HPV negative breast cancer), Lane numbers 6, 10 and 12: Positive cases for HPV-16, Lane numbers 7, 8, 9 and 11: HPV-16 negative cases. N.B.: The amplimer of HPV-16 is 217 bp product and β-globin is 268 bp product (bp: base pair).