nese populations warranted.
suggests that further studies of this type might be
GRANTN. STEMMERMANN,M.D. PO-HUANG CHYOU,PH.D. ABRAHAMM. Y. NOMURA,M.D. Japan-Hawaii Cancer Study Kuakini Medical Center 347 North Kuakini Street Honolulu, Hawaii 96817
Stemmermann GN, Marcus EB, Buist AS, MacLean CJ. Relative impact of smoking and reduced pulmonary function on peptic ulcer risk. Gastroenterology 1989;96:1419-1424. Samloff IM, Stemmermann GN, Heilbrun LK, Nomura A, Elevated serum pepsinogen I and II levels differ as risk factors for duodenal ulcer and gastric ulcer. Gastroenterology 1986;90:570576. Stemmermann GN, Samloff IM, Nomura AMY, Heilbrun LK. Serum pepsinogens I and II and stomach cancer. Clin Chim Acta 1987;163:191-198.
Gastric Carcinoma, Epidermol Growth Factor, and Epidermal Growth Factor Receptor Dear Sir: We read with great interest the article by Pfeiffer (1). We made similar observations (2) using a retrospective immunohistochemical evaluation for epidermal growth factor (EGF) and epidermal growth factor receptor (EGF-R) in 167 cases of benign and malignant gastric disease. A subset of gastric carcinomata, representing about 20% of cases examined, showed increased amounts of EGF and EGF-R in the tumor as well as in adjacent mucosa. Intratumoral levels of EGP and EGF-R were significantly higher than mucosal values. These figures were also significantly higher than the values found in the other gastric carcinomata or in mucosa near peptic ulcers. Thus, overexpression and coexpression of EGF and EGF-R did identify a definite subgroup of gastric carcinoma. In this subgroup, tumor was also found to be more deeply invasive (stage), therefore, implying a different prognosis as well. These observations are important, as the autocrine loop for tumor growth in this subgroup of tumors might be amenable to therapeutic manipulation.
2. Lee N, Wang TC, Clouse RE, DeSchryver-Kecskemeti K, Mucosal thickening adjacent to gastric malignancy: association with epidermal growth factor. Mod Path01 1989;2:397-402.
I welcome the letter from Dr. Lee et al. which addresses an interesting and, I believe, unresolved issue. Regarding a frequent increase in EGF-R number in gastric carcinomata the data by Lee et al. agree with our results and those of other reports (1,2) published since the submission of our manuscript. It should be noted that EGF-R levels determined by immunohistochemistry did not correlate with results from binding studies or Western blots (21, which may, however, relate to the antibody used. Lee et al. (3) and Yasui et al. (2) describe the occurence of increased EGF-like immunoreactivity in a fraction of gastric carcinomata. We have not been able to demonstrate EGF-like immunoreactivity in extracts from normal or malignant gastric tissue, while transdermal growth factor (Y (TGF-a)-like immunoreactivity was demonstrable in extracts of both normal and malignant gastric mucosa (4). TGF-cl-like immunoreactivity was not increased in gastric carcinoma tissue compared with benign mucosa. Similar results were also described by Beauchamps et al. (5). These investigators also showed the occurrence of messenger RNA for TGF-o and EGF-R in human gastric mucosal extracts, while mRNA for EGF was not demonstrable. A third report recently appeared in Nature describing the occurrence of EGF-like material in new cell lineages budding near gastric mucosal ulcers in humans (6). Clearly, EGF-like material is reproducibly demonstrable by immunohistochemistry in the human gastrointestinal tract. However, the nature of this material remains to be established. A reasonable explanation seems to be that of Beauchamps et al. (5) who suggest that the EGF is derived from saliva and may be internalized by EGF receptors. This may also explain increased levels of EGF immunoreactivity in carcinomata expressing increased levels of EGF-R, although such an explanation is not contingent with the hypothesis of autocrine stimulation of cell growth. ANDREAS PFEIFFER,M.D. Department of Internal Medicine Klinikum Bergmannsheil University of Bochum Gilsingstraj3e 14 D-4630 Bochum 1,Germany
ELJNY. LEE,M.D. Department of Pathology Markey Cancer Center University of Kentucky Lexington, Kentucky 40536
TIMOTHYC. WANG, M.D. Division of Gastroenterology Massachusetts General Hospital Boston, Massachusetts 02114 RAY E. CLOUSE,M.D. Division of Gastroenterology Washington University Medical Center St. Louis, Missouri 63110
KATHERINEDESCHRYVER-KJXSKEMETI, M.D. Institute of Pathology Case Western Reserve University Cleveland, Ohio 44 106
1. Pfeiffer A, Rothbauer E, Wiebecke B, Pratschke E, Kramling HJ, Mann K. Increased epidermal growth factor receptors in gastric carcinomas. Gastroenterology 1990;98:961-967.
K, Yonemura Y, Miyakazi I. Immunohistochemical study of epidermal growth factor and epidermal growth factor receptor in gastric carcinoma. Cancer 1989;63:1557-1561, Yasui W, Sumiyoshi H, Hata J, Kameda T, Ochiai A, Ito H, Tahara E. Expression of epidermal growth factor receptor in human gastric and colonic carcinomas. Cancer Res 1988;48:137141. Lee N, Wang TC, Clouse RE, DeSchryver-Kecskemeti K. Mucosal thickening adjacent to gastric malignancy: Association with epidermal growth factor. Mod Path01 1989;2:397-402. Borlinghaus P, Lamerz R, et al. (manuscript in preparation). Beauchamps RD, Barnard JA, McCutchen CM, Charner JA, Coffey RJ, Jr. Localization of transforming growth factor-a and its receptor in gastric mucosal cells. J Clin Invest 199:84:10171023. Wright NA, Pike C, Elisa G. Induction of a novel epidermal growth factor-secreting cell lineage by mucosal ulceration in human gastrointestinal stem cells. Nature 1990;343:82-84.