Expression of growth factors and their receptors in human early colorectal carcinomas: immunohistochemical study

Anticancer Res. Nov-Dec 1995;15(6B):2889-94.


Human colorectal carcinomas have been demonstrated to express a variety of growth factors and their cognate receptors, forming multi-autocrine, juxtacrine and/or paracrine loops. Little information, however, is available on their expression in early colorectal carcinomas in which two genetic pathways exist, i.e. adenoma-carcinoma sequence and de novo carcinoma. This study was conducted in a total of 68 early colorectal carcinomas invading the submucosa, which were subdivided into two categories by the presence of adenomatous components, namely (a) 38 carcinomas with an adenomatous component and (b) 30 carcinoma without an adenomatous component. The tumous were also classified as polypoid, flat elevated and flat depressed type. Formalin-fixed, paraffinembedded specimens were immunostained for epidermal growth factor (EGF), transforming growth factor alpha(TGFalpha), cripto, EGF-receptor(EGFR) and c-ERBB2 gene product. Of the 68 early colorectal carcinomas, EGF, TGF-alpha, cripto, EGFR and c-ERBB2 products were detected at various degrees 24(35%), 50(74%), 31(46%), 11(16%), and 34(50%), respectively. The expression was compared between 35 polypoid carcinomas with an adenoma component (suitable for adenoma-carcinoma sequence), 14 flat carcinomas without an adenoma component (possible de novo carcinomas). A significantly higher incidence (P < 0.05) of expression of the following was noted; TGF-alpha in the polypoid carcinomas with an adenoma component, and EGF and c-ERBB2 gene product in the carcinomas without an adenoma component. There was no significant difference in the incidence of cripto and EGFR, implying common events between two categories. These results indicate that two pathways exist in tumourigenesis, in which the growth factors and their receptors are expressed in different manners. TGF-alpha might play a crucial role in carcinomas arising from adenoma, while EGF and c-ERBB2 gene products are strongly indicative of de novo carcinomas.

Publication types

  • Comparative Study

MeSH terms

  • Adenoma / genetics
  • Adenoma / metabolism
  • Adenoma / pathology
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cell Transformation, Neoplastic / genetics
  • Colonic Polyps / genetics
  • Colonic Polyps / metabolism
  • Colonic Polyps / pathology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Epidermal Growth Factor / biosynthesis
  • Epidermal Growth Factor / genetics
  • ErbB Receptors / biosynthesis
  • ErbB Receptors / genetics
  • GPI-Linked Proteins
  • Gene Expression Regulation, Neoplastic*
  • Growth Substances / biosynthesis*
  • Growth Substances / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Membrane Glycoproteins*
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Receptor, ErbB-2 / biosynthesis
  • Receptor, ErbB-2 / genetics
  • Receptors, Growth Factor / biosynthesis*
  • Receptors, Growth Factor / genetics
  • Transforming Growth Factor alpha / biosynthesis
  • Transforming Growth Factor alpha / genetics


  • GPI-Linked Proteins
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Receptors, Growth Factor
  • TDGF1 protein, human
  • Transforming Growth Factor alpha
  • Epidermal Growth Factor
  • ErbB Receptors
  • Receptor, ErbB-2