Expression of the Tyrosine Kinase Activity Growth Factor Receptors (EGFR, ERB B2, ERB B3) in Colorectal Adenocarcinomas and Adenomas

Abstract

The overexpression of three growth factor receptors: epidermal growth factor receptor (EGFR), ERB B2 and ERB B3 was evaluated immunohistochemically in 77 malignant and 15 benign colorectal neoplasms considering clinicopathological variables (histological structure, grade of differentiation, tumor localization, clinical stage of the disease). The relationship between the coexpression of EGFR-related proteins in individual patients was also evaluated. EGFR expression was revealed in comparable percentages of colorectal adenoma and in adenocarcinoma cases (80% and 70%) while ERB B2 expression was detectable more frequently in adenoma than in adenocarcinoma cases (87% and 54%). The presence of ERB B3 was observed in a higher percentage of adenocarcinoma than adenoma cases (65% and 40%). There was no correlation between the expression of studied tyrosine kinase receptors and histological grade or Dukes’ clinical stage and localization (proximal or distal) of colorectal adenocarcinoma. The incidence of EGFR and ERB B2 expression was higher in tubulovillous (100% for both receptors) than in tubular adenomas (63% and 75%), while the ERB B3 receptor was revealed more frequently in tubular than in tubulovillous neoplasms (50% and 28%). These differences appeared to be statistically nonsignificant. The concomitant expression of two growth factor receptors was observed in a higher percentage of colorectal adenomas than adenocarcinomas, and the coexistence of three growth factors was revealed in comparable percentages in malignant and benign colorectal tumors. Our results support the promotional rather than direct transformational role for the EGFR supergene family in colorectal tumorigenesis. The frequently observed coexpression of more than one EGFR-related protein in colorectal neoplasms indicates the possible cooperation of these receptors in mitogenic signaling transduction, facilitating the development and maintenance of the malignant phenotype.

Phase II study of erlotinib (OSI-774) in patients with metastatic colorectal cancer

“…Epidermal growth factor receptor is overexpressed in many different cancer types, including 60-80% of colon cancers (Porebska et al, 2000), which correlates with a poor prognosis (Mayer et al, 1993). This further supports the hypothesis that inhibition of the EGFR signalling cascade may potentially be therapeutic.…”

Close association between HER-2 amplification and overexpression in human tumors of non-breast origin

“…For example, HER-2 overexpression was shown in 5.7-88.8% of non-small-cell lung cancers 10,11 and 3.0-54% of colon cancers. 12,13 To a smaller extent, this variability is also observed in amplification analysis. Different methods for analysis (Southern blot or fluorescent in situ hybridization (FISH)) and definitions of amplification have resulted in variable frequencies of amplification reported in the literature such as 0-66% in ovarian cancer 14,15 or 6-56.2% in breast cancer.…”

Targeting EGFR and HER-2 with cetuximab- and trastuzumab-mediated immunotherapy in oesophageal squamous cell carcinoma

“…Overexpression of the HER family members has been identified in a variety of human cancers such as gastrointestinal tract (Ghaderi et al, 2002;Kimura et al, 2004), colorectal (Hayashi et al, 1994;Porebska et al, 2000;Ooi et al, 2004), breast (Suo et al, 2002;Witton et al, 2003;Abd El-Rehim et al, 2004;DiGiovanna et al, 2005), lung (Hirsch et al, 2003), prostate (Di Lorenzo et al, 2002), and bladder cancers (Chow et al, 2001;Wester et al, 2002), and is correlated in a wide variety of tumours with the progression (Yarden and Sliwkowski, 2001). In particular, we and others have recently reported that the overexpression of EGFR of oesophageal SCC, partially accounted for by gene amplification, is found in 50 -70% (Itakura et al, 1994;Hanawa et al, 2006), and is indicative of a poor prognosis (Ozawa et al, 1989;Yano et al, 1991).…”