Expression of the tyrosine kinase activity growth factor receptors (EGFR, ERB B2, ERB B3) in colorectal adenocarcinomas and adenomas.

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.