Abstract
We examined the localization of epidermal growth factor (EGF) in 185 specimens of primary human gastric cancer using the avidinbiotin peroxidase complex immunohistochemical method on formalin-fixed paraffin-embedded sections. Thirty-four per cent of the gastric cancer specimens were positive for EGF, which was mainly located in the cytoplasm of the cancer cells and occasionally in the stromal cells, but was not detected in non-cancerous gastric epithelium. Moreover, the presence of EGF in gastric cancer was correlated with gastric wall invasion and lymph node metastasis. EGF was found more often in advanced cancers than in early ones (p<0.01), and also more often in cancers with lymph node metastasis than in those without (p<0.05). The five-year survival of patients with EGF-positive tumors was worse than that of patients with EGF-negative tumors (p<0.05). The presence of EGF in human gastric cancer may thus represent higher malignant potential.
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Choen S. Isolation of mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the newborn animal. J Biol Chem 1962; 237: 1555–1562.
Starkey RH, Cohen S, Orth EN. Epidermal growth factor. Identification of a new hormone in human urine. Science 1975; 189: 800–802.
Hamburger AW, White CP, Brown RW. Effect of epidermal growth factor on proliferation of human tumor cells in soft agar. J Natl Cancer Inst 1981; 67: 825–830.
Singletary SE, Baker FL, Spitzer G, Tucker SL, Tomasovic B, Brock WA, Ajani JA, Kelly AM. Biological effect of epidermal growth factor on thein vitro growth of human tumors. Cancer Res 1987; 47: 403–407.
Kasselberg AG, Orth DN, Gray ME, Stahlman MT. Immunocytochemical localization of human epidermal growth factor/urogastrone in several human tissues. J Histochem Cytochem 1985; 33: 315–322.
Tsukitani K, Tatemoto Y, Noda A, Mori M, Hayashi T, Kato K. Immunohistochemical detection of human epidermal growth factor in submandibular glands and their tumors using a polyclonal antiserum and a monoclonal antibody. Histochem 1987; 87: 293–300.
Mori M, Naito R, Tsukitanbi K, Okada Y, Hayashi T, Kayo K. Immunohistochemical distribution of human epidermal growth factor in salivary gland tumours. Virchows Arch A 1987; 411: 499–507.
Tahara E, Sumiyoshi H, Hata J, Yasui W, Taniyama K, Hayashi T, Nagae S, Sakamoto S. Human epidermal growth factor in gastric carcinoma as a biologic marker of high malignancy. Jpn J Cancer Res (Gann) 1986; 77: 145–152.
Tokunaga A, Onda M, Shimizu Y, Yoshiyuki T, Nishi K, Matsukura N, Tanaka N. Estrogen receptor, estradiol and epidermal growth factor in gastric cancer as biological markers of proliferation and progression. Nippon Geka Gakkai Zasshi (J Jpn Surg Soc) 1987; 88: 1113–1116. (in Japanese with English Abst.)
Borrmann R, Geschwurste des Magen und Duodenums. In: Henke F, Lubarsch O, eds. Handbuch der spezillen pathologischen Anatomie und Histologie. Bd 4/1. Berlin: Verlag von J Springer 1926; 812–1054.
Japanese Research Society for Gastric Cancer. The general rules for the gastric cancer study in surgery and pathology. Jpn J Surg 1981; 11: 127–139.
Laurén P. The two histological main types of gastric carcinoma: Diffuse and so-called intestinal-type carcinoma. Acta Pathol Microbiol Scand 1965; 64: 31–49.
Hirota T, Yamamichi N, Itabashi M, Kitaoka H, Maruyama K, Hirata K, Oguro H, Yamada T. Clinicopathological study of early gastric cancer with submucosal invasion—Relationship between macroscopic and microscopic findings. I to Cho (Stomach and Intestine) 1982; 17: 497–509 (in Japanese with English Abst.)
Tokunaga A, Nishi K, Matsukura N, Tanaka N, Onda M, Shirota A, Asano G, Hayashi K. Estrogen and progesterone receptors in gastric cancer. Cancer 1986; 57: 1376–1379.
Hsu SM, Raine L, Fanger H. Use of avidin-biotin peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabelled antibody (PAP) procedure. J Histochem Cytochem 1981; 29: 577–580.
Brook JSJ. Analytic false positivity with immunohistochemistry. Am J Clin Pathol 1984; 82: 134–135.
Yasui W, Hata J, Yokozaki H, Nakatani H, Ochiai A, Ito H, Tahara E. Interaction between epidermal growth factor and its receptor in progression of human gastric carcinoma. Int J Cancer 1988; 41: 211–217.
Fushida S, Yonemura Y, Sugiyama K, Matsumoto H, Kamata T, Miwa K, Miyazaki I. Human epidermal growth factor (h-EGF) in gastric carcinomas. Nippon Geka Gakkai Zasshi (J Jpn Surg Soc) 1988; 89: 1965–1968. (in Japanese with English Abst.)
Sugiyama K, Yonemura Y, Miyazaki I. Immunohistochemical study of epidermal growth factor receptor in gastric cancer. Cancer 1989; 63: 1557–1561.
Kodama Y, Inokuchi K, Soejima K, Matsusaka T, Okamura T. Growth patterns and prognosis in early gastric carcinoma; Superficially spreading and penetrating growth types. Cancer 1983; 51: 320–326.
Stoscheck CM, King Jr LE. Role of epidermal growth factor in carcinogenesis. Cancer Res 1986; 46: 1030–1037.
Goustin AS, Leof EB, Shipley GD, Moses HL. Growth factors and cancer. Cancer Res 1986; 46: 1015–1029.
Townsend JR CM, Beauchamp RD, Singh P, Thompson JC. Growth factors and intestinal neoplasms. Am J Surg 1988; 155: 526–536.
Yoshiyuki T, Shimizu Y, Onda M, Tokunaga A, Kiyama T, Nishi K, Matsukura N, Tanaka N, Asano G. Immunohistochemical demonstration of epidermal growth factor in human gastric cancer xenografts in nude mice. Cancer 1990; 65: 953–957.
Koch JH, Fifis T, Bender VJ, Moss BA. Molecular species of epidermal growth factor carrying immunosuppressive activity. J Cell Biochem 1984; 25: 45–59.
Takeda T, Grollman A. Inhibitory action of submaxillary gland on thymus and lymphoid tissues of the mouse. Am J Physiol 1968; 215: 1337–1342.
Ming SC. Gastric carcinoma. A pathobiological classification. Cancer 1977; 39: 2475–2485.
Tahara E, Ito H, Nakagami K, Shimamoto F, Yamamoto M, Sumii K. Scirrhous argyrophil cell carcinoma of the stomach with multiple production of polypeptide hormones, amine, CEA, lysozyme, and HCC. Cancer 1982; 49: 1904–1915.
Fitzpatrick S, Brightwell J, Wittliff JL, Barrows GH, Schultz GS. Epidermal growth factor binding by breast tumor biopsies and relationships to estrogen receptor and progestin receptor levels. Cancer Res 1984; 44: 3448–3453.
Yamamoto T, Kamata N, Kawano H, Shimizu S, Kuroki T, Toyoshima K, Rikimaru K, Nomura N, Ishizaki R, Pastan I, Gamou S, Shimizu N. High incidence of amplification of the epidermal growth factor receptor gene in human squamous carcinoma cell lines. Cancer Res 1986; 46: 414–416.
Bradley SJ, Garfinkle G, Walker E, Salem R, Chen LB, Steele Jr G. Increased expression of the epidermal growth factor receptor on human colon carcinoma cells. Arch Surg 1986; 121: 1242–1247.
van de Vijver MJ, Peterse JI, Mooi WJ, Wisman P, Lomans J, Dalesio O, Nusse R. New-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer. New Eng J Med 1988; 319: 1239–1245.
Tokunaga A, Onda M, Kiyama T, Yoshiyuki T, Shimizu Y, Nishi K, Yagi K, Matsukura N, Tanaka N, Moriyama Y, Asano G. Epidermal growth factor receptor in human gastric cancer and xenografts in nude mice. Proc 80th Ann Meet Amer Assoc Cancer Res 1989; 244.
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Onda, M., Tokunaga, A., Nishi, K. et al. The correlation of epidermal growth factor with invasion and metastasis in human gastric cancer. The Japanese Journal of Surgery 20, 269–274 (1990). https://doi.org/10.1007/BF02470660
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DOI: https://doi.org/10.1007/BF02470660