Summary
Using the monoclonal antibody EGFR1, the expression of epidermal growth factor receptor (EGFR) was investigated immunohistochemically in normal colonic mucosa distant from and adjacent to colonic neoplasms, in 25 adenomas and in 144 unselected colorectal carcinomas. EGFR expression was an inconsistant phenomenon in each of these conditions. It was not expressed in 23/44 non-neoplastic mucosa specimens distant from and in 26/44 mucosae adjacent to colon tumours; 15/25 adenomas and 71 (49.3%) of the carcinomas failed to contain detectable amounts of EGFR. In contrast, large amounts of EGFR were found in 4 non-neoplastic mucosae at both locations, in 3 adenomas and in 11 (7.6%) carcinomas. The remaining cases showed complex patterns of EGFR-expression. In comparing mucosae close to and distant from a colonic tumour, only minor differences in EGFR content were observed. The intra-individual comparison of the mode of EGFR expression in non-neoplastic and neoplastic epithelium revealed an overexpression of EGFR in carcinomas in about one third of the 44 cases examined. One third showed no obvious differences, and one third showed lower levels of EGFR expression within the tumour. We conclude that the mode of EGFR expression in normal and neoplastic colon epithelium is variable and reflective of inter-individual constitutive differences rather than of abnormalities in gene regulation. Statistical analysis failed to reveal correlations between the mode of EGFR expression and tumour grade, type or Dukes stage.
Similar content being viewed by others
References
Al-Nafussi AI, Wright NA (1982) The effect of epidermal growth factor (EGF) on cell proliferation of the gastrointestinal mucosa in rodents. Virchows Arch [A] 40:63–69
Berger MS, Greenfield C, Gullick WJ, Haley J, Downward J, Neal DE, Harris AL, Waterfield MD (1987a) Evaluation of epidermal growth factor receptors in bladder tumours. Br J Cancer 56:533–537
Berger MS, Gullick WJ, Greenfield C, Evans S, Addis BJ, Waterfielde MD (1987b) Epidermal growth factor receptors in lung tumours. J Pathol 152:297–307
Blay J, Brown KD (1985) Functional receptors for epidermal growth factor in an epithelial-cell line derived from the rat small intestine. Biochem J 225:85–94
Burgess AW (1989) Epidermal growth factor and transforming growth factor α. Br Med Bull 45:401–424
Carpenter G (1983) The biochemistry and physiology of the receptor-kinase for epidermal growth factor. Mol Cell Endocrinol 31:1–19
Carpenter G (1987) Receptors for epidermal growth factor and other polypeptide mitogens. Annu Rev Biochem 56:881–914
Carpenter G, Cohen S (1976)125I-labeled human epidermal growth factor: binding, internalization and degradation in human fibroblasts. J Cell Biol 71:159–171
Carpenter G, Cohen S (1979) Epidermal growth factor. Annu Rev Biochem 48:193–216
Cohen S, Fava RA (1985) Internalization of functional epidermal growth factor: receptor/kinase complexes in A431-cells. J Biol Chem 260:12351–12358
Cohen S, Taylor JM (1974) Epidermal growth factor: chemical and biological characterization. Recent Prog Horm Res 30:533–550
Damjanov I, Mildner B, Knowles BB (1986) Immunohistochemical localization of the epidermal growth factor receptor in normal human tissues. Lab Invest 55:588–592
Downward J, Yarden Y, Mayes E, Scrace G, Totty N, Stockwell P, Ullrich A, Schlessinger J, Waterfield MD (1984) Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 307:521–527
Eker P (1989) Effects of epidermal growth factor, fibroblast growth factor, retinoic acid and serum on anchorage-dependent and anchorage-independent growth of HRRT cells. Eur J Cancer Clin Oncol 25:499–504
Forgue-Lafitte M-E, Laburthe M, Chamblier M-C, Moody A, Rosselin G (1980) Demonstration of specific receptors for EGF-Urogastrone in isolated rat intestinal epithelial cells. FEBS Lett 114:243–246
Glenney JR, Chen WS, Lazar CS, Walton GM, Zokas LM, Rosenfeld MG, Gill GN (1988) Ligand-induced endocytosis of the EGF receptor is blocked by mutational inactivation and by microinjection of anti-phosphotyrosine antibodies. Cell 52:675–684
Gullick WJ, Marsden JJ, Whittle N, Ward B, Bobrow L, Waterfield MD (1986) Expression of epidermal growth factor receptors on human cervical, ovarian, and vulval carcinomas. Cancer Res 46:285–292
Gusterson B, Cowley G, Smith JA, Ozanne B (1984) Cellular localization of human epidermal growth factor receptor. Cell Biol Int Rep 8:649–658
Gusterson B, Cowley G, McIlhinney J, Ozanne B, Fisher C, Reeves B (1985) Evidence for increased epidermal growth factor receptors in human sarcomas. Int J Cancer 36:689–693
Hunts J, Ueda M, Ozawa S, Abe O, Pastan I, Shimizu N (1985) Hyperproduction and gene amplification of the epidermal growth factor receptor in squamous cell carcinomas. Jpn J Cancer Res [Gann] 76:663–666
Ishitoya J, Toriyama M, Oguchi N, Kitamura K, Ohshima M, Asano K, Yamamoto T (1989) Gene amplification and overexpression of EGF receptor in squamous cell carcinomas of the head and neck. Br J Cancer 59:559–562
Joh T, Itoh M, Katsumi K, Yokoyama T, Miyamoto T, Imai S, Ikeda K, Matsusako K, Takeuchi T, Kato T, Tanaka R (1987) Immunoreactive epidermal growth factor in mouse digestive organs. Use of a sensitive enzyme immunoassay. Acta Endocrinol (Copenh) 115:203–210
Kasselberg AG, Orth DN, Gray ME, Stahlman MT (1985) Immunocytochemical localization of human epidermal growth factor/urogastrone in several human tissues. J Histochem Cytochem 33:315–322
Möller P, Mechtersheimer G, Kaufmann M, Momburg F, Mattfeldt T, Otto HF (1989) Expression of epidermal growth factor receptor in benign and malignant tumours of the breast. Virchows Arch [A] 414:157–164
Moolenaar WH, Bierman AJ, Tilly BC, Verlaan I, Defize LHK, Honegger AM, Ullrich A, Schlessinger J (1988) A point mutation at the ATP-binding site of the EGF-receptor abolishes signal transduction. EMBO J 7:707–710
Neal DE, Marsh C, Benett MK, Abel PD, Hall RR, Sainsbury JRC, Harris AL (1985) Epidermal-growth-factor receptors in human bladder cancer: comparison of invasive and superficial tumours. Lancet ii:366–368
Perosio PM, Brooks JJ (1989) Expression of growth factors and growth factor receptors in soft tissue tumors. Implications for the autocrine hypothesis. Lab Invest 60:245–253
Poulsen SS, Nexo E, Olsen PS, Hess J, Kirkegaard P (1986) Immunohistochemical localization of epidermal growth factor in rat and man. Histochemistry 85:389–394
Rall LB, Scott J, Bell GJ, Niall H, Coghlan JC (1985) Mouse prepro-epidermal growth factor synthesis by the kidney and other tissues. Nature 313:228–231
Reifenberger G, Prior R, Deckert M, Wechsler W (1989) Epidermal growth factor receptor expression and growth fraction in human tumours of the nervous system. Virchows Arch A 414:147–155
Reubi JC, Horisberger U, Lang W, Koper JW, Braakman R, Lamberts SWJ (1989) Coincidence of EGF receptors and somatostatin receptors in meningeomas but inverse, differentiation-dependent relationship in glial tumors. Am J Pathol 134:337–344
Rothbauer E, Mann K, Wiebecke B, Borlinghaus P, Lamerz R, Pratschke E, Krämling H-J, Pfeiffer A (1989) Epidermal growth factor receptors and epidermal growth factor-like activity in colorectal mucosa, adenomas and carcinomas. Klin Wochenschr 67:518–523
Sainsbury JRC, Nicholson S, Angus B, Farndon JR, Malcolm AJ, Harris AL (1988) Epidermal growth factor receptor status of histological sub-types of breast cancer. Br J Cancer 58:458–460
Shimizu N, Kondo I, Gamou S, Belizadin MA, Shimizu Y (1984) Genetic analysis of hyperproduction of epidermal growth factor receptors in human epidermoid carcinoma A431 cells. Somatic Cell Mol Genet 10:45–49
Squinto SP, Block AL, Doucet JP (1989) Epidermal growth factor induction of cellular proliferation and protooncogene expression in growth-arrested rat H4IIE hepatoma cells: role of cyclic adenosine monophosphate. Mol Endocrinol 3:433–446
Sugiyama K, Yonemura Y, Miyazaki I (1989) Immunohistochemical study of epidermal growth factor and epidermal growth factor receptor in gastric carcinoma. Cancer 63:1557–1561
Toi M, Hamada Y, Nakamura T, Mukeida H, Suehiro S, Wada T, Toge T, Niimoto M, Hattori T (1989) Immunocytochemical and biochemical analysis of epidermal growth factor receptor expression in human breast cancer tissues: relationship to estrogen receptor and lymphatic invasion. Int J Cancer 43:220–225
van't Hof RJ, Defize LHK, Nuijdens R, de Brabander M, Verklej AJ, Boonstra J (1989) Dynamics of epidermal growth factor receptor internalization studies by Nanovid light microscopy and electron microscopy in combination with immunogold labeling. Eur J Cell Biol 48:5–13
Wahl MT, Nishibe S, Suh P-G, Rhee SG, Carpenter G (1989) Epidermal growth factor stimulates tyrosine phosphorylation of phospholipase C-II independently of receptor internalization and extracellular calcium. Proc Natl Acad Sci USA 86:1568–1572
Waterfield MD, Mayes ELV, Stroobant P, Bennet PLP, Young S, Goodfellow PN, Banting GS, Ozanne B (1982) A monoclonal antibody of the human epidermal growth factor receptor. J Cell Biochem 20:149–161
Yamamoto T, Kamata N, Kawano H, Shimizu S, Kurochi T, Toyoshima K, Rikimaru K, Nomura N, Ishizaki R, Pastan I, Gamou S, Shimizu N (1986) High incidence of amplification of the epidermal growth factor receptor gene in human squamous carcinoma cell lines. Cancer Res 46:414–416
Yasui W, Hata J, Yokozaki H, Nakatani H, Ochiai A, Ito H, Tahara E (1988a) Interaction between epidermal growth factor and its receptor in progression of human gastric carcinoma. Int J Cancer 41:211–217
Yasui W, Sumiyoshi H, Hata J, Kameda T, Ochiai A, Tahara E (1988b) Expression of epidermal growth factor receptor in human gastric and colonic carcinomas. Cancer Res 48:137–141
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Koretz, K., Schlag, P. & Möller, P. Expression of epidermal growth factor receptor in normal colorectal mucosa, adenoma, and carcinoma. Vichows Archiv A Pathol Anat 416, 343–349 (1990). https://doi.org/10.1007/BF01605295
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01605295