Abstract
Epidermal growth factor (EGF), its related peptide transforming growth factor (TGF-alpha) and their common receptor (EGFR) have been implicated in the control of cell proliferation and differentiation in the gastrointestinal epithelium and may play an important role in gastric carcinogenesis. We compared the immunohistochemical expression and topographic distribution of these peptides using Western blot analysis in gastric carcinoma precursor lesions and in non-cancer tissue. We observed: (i) increased and extended expression of TGF-alpha in normal mucosa and hyperplasia in carcinoma fields compared with non-cancer controls; (ii) increased expression of EGFR in intestinal metaplasia (IM) from carcinoma fields compared with controls; (iii) EGF expression was not detected in normal mucosa and only weakly in IM; (iv) coexpression of TGF-alpha/EGFR and EGF/EGFR was higher in intestinal metaplasia in carcinoma fields than in non-cancer controls. We conclude that altered expression of TGF-alpha/EGFR is associated with morphological changes during gastric carcinogenesis. In this regard increased expression of TGF-alpha is a very early event which is subsequently followed by up-regulation of EGFR and this has important biological and clinical implications.
Full text
PDF![30](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/239e/2033456/ed6b54f7d8ab/brjcancer00047-0032.png)
![31](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/239e/2033456/c9c7769c13ef/brjcancer00047-0033.png)
![32](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/239e/2033456/39d3393f8f21/brjcancer00047-0034.png)
![33](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/239e/2033456/6a2e7cb70d95/brjcancer00047-0035.png)
![34](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/239e/2033456/e223d6d2fb30/brjcancer00047-0036.png)
![35](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/239e/2033456/f893ba2f0131/brjcancer00047-0037.png)
![36](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/239e/2033456/75b9c61e463a/brjcancer00047-0038.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Correa P. A human model of gastric carcinogenesis. Cancer Res. 1988 Jul 1;48(13):3554–3560. [PubMed] [Google Scholar]
- Di Marco E., Pierce J. H., Aaronson S. A., Di Fiore P. P. Mechanisms by which EGF receptor and TGF alpha contribute to malignant transformation. Nat Immun Cell Growth Regul. 1990;9(3):209–221. [PubMed] [Google Scholar]
- Filipe M. I., Jankowski J. Growth factors and oncogenes in Barrett's oesophagus and gastric metaplasia. Endoscopy. 1993 Nov;25(9):637–641. doi: 10.1055/s-2007-1010421. [DOI] [PubMed] [Google Scholar]
- Filipe M. I., Mendes R., Lane D. P., Morris R. W. Assessment of proliferating cell nuclear antigen expression in precursor stages of gastric carcinoma using the PC10 antibody to PCNA. Histopathology. 1993 Apr;22(4):349–354. doi: 10.1111/j.1365-2559.1993.tb00134.x. [DOI] [PubMed] [Google Scholar]
- Filipe M. I., Muñoz N., Matko I., Kato I., Pompe-Kirn V., Jutersek A., Teuchmann S., Benz M., Prijon T. Intestinal metaplasia types and the risk of gastric cancer: a cohort study in Slovenia. Int J Cancer. 1994 May 1;57(3):324–329. doi: 10.1002/ijc.2910570306. [DOI] [PubMed] [Google Scholar]
- Jain S., Filipe M. I., Gullick W. J., Linehan J., Morris R. W. c-erbB-2 proto-oncogene expression and its relationship to survival in gastric carcinoma: an immunohistochemical study on archival material. Int J Cancer. 1991 Jul 9;48(5):668–671. doi: 10.1002/ijc.2910480506. [DOI] [PubMed] [Google Scholar]
- Jankowski J. Altered gene expression of growth factors and their receptors during esophageal tumorigenesis. Gastroenterol Clin Biol. 1994;18(1 Pt 2):D40–D45. [PubMed] [Google Scholar]
- Jankowski J., al-Rawi H. J., Johnston D. A., Hopwood D., Filipe M. I., Coghill G., Wormsley K. G. Growth regulatory peptides in gastric mucosa. Clin Sci (Lond) 1992 May;82(5):581–587. doi: 10.1042/cs0820581. [DOI] [PubMed] [Google Scholar]
- LAUREN P. THE TWO HISTOLOGICAL MAIN TYPES OF GASTRIC CARCINOMA: DIFFUSE AND SO-CALLED INTESTINAL-TYPE CARCINOMA. AN ATTEMPT AT A HISTO-CLINICAL CLASSIFICATION. Acta Pathol Microbiol Scand. 1965;64:31–49. doi: 10.1111/apm.1965.64.1.31. [DOI] [PubMed] [Google Scholar]
- Lemoine N. R., Jain S., Silvestre F., Lopes C., Hughes C. M., McLelland E., Gullick W. J., Filipe M. I. Amplification and overexpression of the EGF receptor and c-erbB-2 proto-oncogenes in human stomach cancer. Br J Cancer. 1991 Jul;64(1):79–83. doi: 10.1038/bjc.1991.243. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Martin H. M., Filipe M. I., Morris R. W., Lane D. P., Silvestre F. p53 expression and prognosis in gastric carcinoma. Int J Cancer. 1992 Apr 1;50(6):859–862. doi: 10.1002/ijc.2910500604. [DOI] [PubMed] [Google Scholar]
- Nasim M. M., Thomas D. M., Alison M. R., Filipe M. I. Transforming growth factor alpha expression in normal gastric mucosa, intestinal metaplasia, dysplasia and gastric carcinoma--an immunohistochemical study. Histopathology. 1992 Apr;20(4):339–343. doi: 10.1111/j.1365-2559.1992.tb00991.x. [DOI] [PubMed] [Google Scholar]
- Parsonnet J., Friedman G. D., Vandersteen D. P., Chang Y., Vogelman J. H., Orentreich N., Sibley R. K. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991 Oct 17;325(16):1127–1131. doi: 10.1056/NEJM199110173251603. [DOI] [PubMed] [Google Scholar]
- Pignatelli B., Malaveille C., Bartsch H. Intragastric mutagens and lowered anti-oxidant defence as risk factors for gastric cancer. Eur J Cancer Prev. 1993 Jun;2 (Suppl 2):9–11. doi: 10.1097/00008469-199306000-00003. [DOI] [PubMed] [Google Scholar]
- Riddell R. H., Goldman H., Ransohoff D. F., Appelman H. D., Fenoglio C. M., Haggitt R. C., Ahren C., Correa P., Hamilton S. R., Morson B. C. Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications. Hum Pathol. 1983 Nov;14(11):931–968. doi: 10.1016/s0046-8177(83)80175-0. [DOI] [PubMed] [Google Scholar]
- Rokkas T., Filipe M. I., Sladen G. E. Detection of an increased incidence of early gastric cancer in patients with intestinal metaplasia type III who are closely followed up. Gut. 1991 Oct;32(10):1110–1113. doi: 10.1136/gut.32.10.1110. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Soman N. R., Correa P., Ruiz B. A., Wogan G. N. The TPR-MET oncogenic rearrangement is present and expressed in human gastric carcinoma and precursor lesions. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4892–4896. doi: 10.1073/pnas.88.11.4892. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tahara E. Growth factors and oncogenes in human gastrointestinal carcinomas. J Cancer Res Clin Oncol. 1990;116(2):121–131. doi: 10.1007/BF01612665. [DOI] [PubMed] [Google Scholar]
- Tahara E. Molecular mechanism of stomach carcinogenesis. J Cancer Res Clin Oncol. 1993;119(5):265–272. doi: 10.1007/BF01212724. [DOI] [PubMed] [Google Scholar]
- Tohdo H., Yokozaki H., Haruma K., Kajiyama G., Tahara E. p53 gene mutations in gastric adenomas. Virchows Arch B Cell Pathol Incl Mol Pathol. 1993;63(3):191–195. doi: 10.1007/BF02899260. [DOI] [PubMed] [Google Scholar]
- Yonemura Y., Sugiyama K., Fushida S., Kamata T., Ohoyama S., Kimura H., Yamaguchi A., Miyazaki I. Tissue status of epidermal growth factor and its receptor as an indicator of poor prognosis in patients with gastric cancer. Anal Cell Pathol. 1991 Nov;3(6):343–350. [PubMed] [Google Scholar]
- Yonemura Y., Takamura H., Ninomiya I., Fushida S., Tsugawa K., Kaji M., Nakai Y., Ohoyama S., Yamaguchi A., Miyazaki I. Interrelationship between transforming growth factor-alpha and epidermal growth factor receptor in advanced gastric cancer. Oncology. 1992;49(2):157–161. doi: 10.1159/000227031. [DOI] [PubMed] [Google Scholar]