Summary
The c-erbB-2 (HER-2/neu) protein is a membrane glycoprotein growth factor receptor that has molecular homology with the epidermal growth factor receptor (EGFR). To investigate the relationship between the expression of c-erbB-2 protein and EGFR in the tissues of the human female genital tract and in the placenta, we examined the immunohistochemical reactivity of monoclonal antibodies against both of these proteins. In the müllerian-derived genital tract, epithelial cells of the fallopian tube, endometrium, and endocervix showed reactivity for c-erbB-2 protein, whereas reactivity for EGFR was distributed mainly in the stromal cells throughout the menstrual cycle and during pregnancy. In addition, the staining intensity for EGFR in the endometrial stroma increased with its decidualization. In the exocervical squamous epithelium, basal cells were cerbB-2 protein-negative and EGFR-positive, but the more differentiated squamous cells of the intermediate layer were c-erbB-2 protein-positive and EGFR-negative. In the placental tissues, cytotrophoblasts and syncytiotrophoblasts of the chorionic villi were c-erbB-2 protein-negative and EGFR-positive. In contrast, intermediate trophoblasts in the extravillous space were c-erbB-2 protein-positive and EGFR-negative. Thus, there is an inverse relationship between the expression of c-erbB-2 protein and EGFR in the tissues of the female genital tract and in the placenta. This suggests that there may be a regulatory mechanism(s) for the expression of both proteins that is associated with the differentiation and/or function of cells in the female genital tract and the placenta.
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References
Benirschke K, Kaufmann P (1990) Nonvillous parts of the placenta. In: Pathology of the human placenta, 2nd edn. Springer, Berlin Heidelberg New York, p 244
Berchuck A, Soisson AP, Olt GJ, Soper JT, Clarke-Pearson DL, Bast RC, McCarty KS (1989) Epidermal growth factor receptor expression in normal and malignant endometrium. Am J Obstet Gynecol 161:1247–1252
Berchuck A, Kamel A, Whitaker R, Kerns B, Olt G, Kinney R, Soper JT, Dodge R, Clarke-Pearson DL, Marks P, McKenzie S, Yin S, Bast RC (1990) Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res 50:4087–4091
Berchuck A, Rodriguez G, Kinney RB, Soper JT, Dodge RK, Clarke-Pearson DL, Bast RC (1991) Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease. Am J Obstet Gynecol 164:15–21
Carson SA, Chase R, Ulep E, Scommegna A, Benveniste R (1983) Ontogenesis and characteristics of epidermal growth factor receptors in human placenta. Am J Obstet Gynecol 147:932–939
Chegini N, Rao CV, Wakim N, Sanfilippo J (1986) Binding of125I-epidermal growth factor in human uterus. Cell Tissue Res 246:543–548
Cohen JA, Weiner DB, More KF, Kokai Y, Williams WV, Maguire HC, LiVolsi VA, Greene MI (1989) Expression pattern of theneu (NGL) gene-encoded growth factor receptor protein (p185neu) in normal and transformed epithelial tissues of the digestive tract. Oncogene 4:81–88
Coussens L, Yang-Feng TL, Liao YU, Chen L, Gray A, McGrath J, Seeburg PH, Libermann TA, Schlessinger J, Francke U, Levinson U, Ullrich A (1985) Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location withneu oncogene. Science 230:1132–1139
Fukushige S, Matsubara K, Yoshida M, Sasaki M, Suzuki T, Semba K, Toyoshima K, Yamamoto T (1986) Localization of a novel v-erbB-related gene, c-erbB-2, on human chromosome 17 and its amplification in a gastric cancer cell line. Mol Cell Biol 6:955–958
Gosseye S, Fox H (1984) An immunohistological comparison of the secretory capacity of villous and extravillous trophoblast in the human placenta. Placenta 5:329–348
Gullick WJ, Berger MS, Bennett PLP, Rothbard JB, Waterfield MD (1987) Expression of the c-erbB-2 protein in normal and transformed cells. Int J Cancer 40:246–254
Haldane JS, Hird V, Hughes CM, Gullick WJ (1990) c-erbB-2 oncogene expression in ovarian cancer. J Pathol 162:231–237
Iglehart JD, Kraus MH, Langton BC, Huper G, Kerns BJ, Marks JR (1990) IncreasederbB-2 gene copies and expression in multiple stages of breast cancer. Cancer Res 50:6701–6707
King CR, Kraus MH, Aaronson SA (1985) Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science 229:974–976
Kurman RJ, Main CS, Chen HC (1984) Intermediate trophoblast: a distinctive form of trophoblast with specific morphological, biochemical and functional features. Placenta 5:349–370
Lawrence WD, Shingleton HM (1980) Early physiologic squamous metaplasia of the cervix: light and electron microscopic observations. Am J Obstet Gynecol 137:661–671
Maguire HC, Jaworsky C, Cohen JA, Hellman M, Weiner DB, Greene MI (1989) Distribution of neu (c-erbB-2) protein in human skin. J Invest Dermatol 89:786–790
Maruo T, Mochizuki M (1987) Immunohistochemical localization of epidermal growth factor andmyc oncogene product in human placenta: implication for trophoblast proliferation and differentiation. Am J Obstet Gynecol 156:721–727
Mori S, Akiyama T, Morishita Y, Shimizu S, Sakai K, Sudoh K, Toyoshima K, Yamamoto T (1987) Light and electron-microscopical demonstration of c-erbB-2 gene product-like immunoreactivity in human malignant tumors. Virchows Arch [B] 54:8–15
Mori S, Akiyama T, Yamada Y, Morishita Y, Sugawara I, Toyoshima K, Yamamoto T (1989) C-erbB-2 gene product, a membrane protein commonly expressed on human fetal epithelial cells. Lab Invest 61:93–97
Noyes RW, Hertig AT, Rock J (1950) Dating the endometrial biopsy. Fertil Steril 1:3–10
Oberg KC, Brown A, Carpenter G (1990) Growth factor receptors: the epidermal growth factor as a model. In: Habenicht A (ed) Growth factors, differentiation factors, and cytokines, Springer, Berlin Heidelberg New York, p 3
Parmley T (1987) Embryology of the female genital tract. In: Kurman RJ (ed) Blaustein's pathology of the female genital tract. 3rd edn. Springer, Berlin Heidelberg New York, p 1
Press MF, Cordon-Cardo C, Slamon DJ (1990) Expression of the HER-2/neu proto-oncogene in normal human adult and fetal tissues. Oncogene 5:953–962
Rao CV, Ramani N, Chegini N, Stadig BK, Carman FR, Woost PG, Schultz GS, Cook CL (1985) Topography of human placental receptors for epidermal growth factor. J Biol Chem 260:1705–1710
Schechter AL, Stern DF, Vaidyanathan L, Decker SJ, Drebin JA, Greene MI, Weinberg RA (1984) Theneu oncogene: anerb-B-related gene encoding a 185000-Mr tumour antigen. Nature 312:513–516
Semba K, Kamata N, Toyoshima K, Yamamoto T (1985) A v-erbB-related proooncogene, c-erbB-2, distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. Proc Natl Acad Sci USA 82:6497–6501
Sheets EE, Tsibris JCM, Cook NI, Virgin SD, DeMay RM, Spellacy WN (1985) In vitro binding of insulin and epidermal growth factor to human endometrium and endocervix. Am J Obstet Gynecol 153:60–65
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, Mcguire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–181
Taketani Y, Mizuno M (1988) Cyclic changes in epidermal growth factor receptor in human endometrium during menstrual cycle. Endocrinol Jpn 35:19–25
Tyson FL, Soper JT, Daly L, Fowler WC Jr, Haskill JS, Kraus MH, Bast RC Jr (1988) Overexpression and amplification of the C-erbB-2HER 2/neu) proto-oncogene in epithelial Ovarian tumors and cell lines. Proc Am Assoc Cancer Res 29:471
Weidner U, Peters S, Strohmeyer T, Hussnatter R, Ackermann R, Sies H (1990) Inverse relationship of epidermal growth factor receptor and HER2/neu gene expression in human renal cell carcinoma. Cancer Res 50:4504–4509
Yamamoto T, Ikawa S, Akiyama T, Semba K, Nomura N, Miyajima N, Saito T, Toyoshima K (1986) Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature 319:230–234
Yamamoto T, Nishiyama M, Yanoh K, Naka Y, Naka A, Sugiyama Y (1989) Regulation of human endometrial and decidual cell functions: role of epidermal growth factor in the decidualization. Prog Clin Biol Res 294:413–424
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Wang, D.p., Fujii, S., Konishi, I. et al. Expression of c-erbB-2 protein and epidermal growth factor receptor in normal tissues of the female genital tract and in the placenta. Vichows Archiv A Pathol Anat 420, 385–393 (1992). https://doi.org/10.1007/BF01600509
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DOI: https://doi.org/10.1007/BF01600509