Summary
Seventy specimens of normal endometrium (n=13) and cervix (n=12), endometrial hyperplasia (n=4), cervical dysplasia (n=20), endometrial (n=11) and cervical carcinoma (n=8) and uterine metastases of mammary carcinomas (n=2) have been analysed for cerbB-2 expression with immunohistochemistry employing a monoclonal anti ERBB-2 antibody and Northern-blot hybridization using single stranded RNA probes. In comparison with the c-erbB-2 mRNA expression level found in normal samples, two advanced and poorly differentiated endometrial adenocarcinomas (FIGO IV) and two ductal mammary carcinomas which had metastasized to the uterus, together with three carcinomas in situ of the cervix, showed c-erbB-2 enhanced transcription level. All other endometrial samples including adenomatous hyperplasia and nine endometrial carcinomas (FIGO I), and all other lesions of squamous epithelial origin displayed transcriptional activities at or below the baseline level. Immunohistochemical study of ERBB-2 protein expression showed staining in most samples, although different in distribution and intensity. Staining of endometrial glands was seen in unevenly distributed cells or cell clusters. In contrast, for endocervical glands, labelling was observed distinctly on basally located cells (reserve cells) and at the subapical side of luminal cells. Faint labelling of the basal cell layer was also observed in squamous epithelia. It was more pronounced in severe cervical dysplasia and carcinoma in situ. In carcinomas of glandular origin, dedifferentiation was accompanied by an increase in cytoplasmic labelling, whereas the intensity of staining was not related to differentiation in squamous cell carcinomas. While data derived from Northern blots are suggestive of cerbB-2 overexpression to indicate an advanced and dedifferentiated state of tumours of glandular origin, staining with an anti-ERBB-2 antibody occurred in both normal and atypical squamous and glandular epithelia and may indicate regular proliferation and/or differentiation-associated events.
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References
Bargmann CI, Hung M-C, Weinberg RA (1986) The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature 319:226–230
Brumm C, Schulze C, Charels K, Morohoshi T, Klöppel G (1989) The significance of alpha-fetoprotein and other tumour markers in differential immunocytochemistry of primary liver tumours. Histopathology 14:503–513
Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ (1979) Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochem 18:5294–5299
Coussens L, Yang-Feng TL, Liao Y-C, Chen E, Gray A, McGrath J, Seeburg PH, Libermann TA, Schlessinger J, Francke U, Levinson A, Ullrich A (1985) Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogne. Science 230:1132–1139
Dallenbach-Hellweg G (1981) Histopathology of the endometrium. Springer, Berlin Heidelberg New York, p 1
De Potter CR, van Daele S, van de Vijver MJ, Pauwels C, Maertens G, de Boever J, Vandekerckhove D, Roels H (1989) The expression of the neu oncognene product in breast lesions and in normal fetal and adult human tissues. Histopathology 15:351–362
Guerin M, Gabillot M, Mathieu M-C, Travagli J-P, Spielmann M, Andrieu N, Riou G (1989) Structure and expression of c-erbB-2 and EGF receptor genes in inflammatory and non-inflammatory breast cancer: prognostic significance. Int J Cancer 43:201–208
Heintz NH, Leslie KO, Rogers LA, Howard PL (1990) Amplification of the c-erbB-2 oncogene and prognosis of breast adenocarcinoma. Arch Pathol Lab Med 114:160–163
Lessey BA, Killam AP, Metzger DA, Haney AF, Greene GL, McCarty Jr KS (1988) Immunohistochemical analysis of human uterine estrogen and progesterone receptors throughout the menstrual cycle. J Clin Endo Metabl 67:334–340
Lemoine NR, Staddon S, Dickson C, Barnes DM, Gullick WJ (1990) Absence of activating transmembrane mutations in the c-erbB-2 proto-oncogene in human breast cancer. Oncogene 5:237–239
Löning T, Kühler C, Caselitz J, Stegner H-E (1983) Keratin and tissue polypeptide antigen profiles of the cervical mucosa. Int J Gyn Pathol 2:105–112
Marx D, Schauer A, Reiche C, May A, Ummenhofer L, Reles A (1990) C-erbB2 expression in correlation to other biological parameters in breast cancer. J Cancer Res Clin Oncol 116:15–20
Perbal B (1988) A practical guide to molecular cloning. Second edition. John Wiley, New York Chichester Brisbane Toronto, pp 520–522
Schlechter AL, Hung M-C, Vaidyanathan L, Weinberg RA, Yang-Feng TL, Francke U, Ullrich A, Coussens L (1985) The neu gene: an erbB-homologous gene distinct from an unlinked to the gene encording the EGF Receptor. Science 229:976–978
Seeger RC, Brodeur GM, Sather H, Dalton A, Siegel SE, Wong KY, Hammond D (1985) Association of multiple copies of the N-myc oncogene with rapid progression of neuro-blastomas. N Engl J Med 313:1111–1117
Semba K, Kamata N, Toyoshima K, Yamamoto T (1985) A verbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. Biochemistry 82:6497–6501
Shtivelman E, Lifshitz B, Gali RP, Canaani E (1985) Fused transcript of abl and bcr genes in chronic myelogenous leukemia. Nature 315:550–554
Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A, Press MF (1989) Studies of the HER-2/neu protooncogne in human breast and ovarian cancer. Science 244:707–712
Stern DF, Hefferman PA, Weinberg RA (1986) p185, a product of the neu proto-oncogne, is a receptorlike protein associated with tyrosine kinase activity. Mol Cell Biol 6:1729–1740
Tauchi K, Hori S, Itoh H, Osamura RY, Tokuda Y, Tajima T (1989) Immunohistochemical studies on oncogne products (c-erbB-2, EGFR, c-myc) and estrogen receptor in benign and malignant breast lesions. Virchows Archiv A Pathol Anat 416:65–73
Van de Vijver MJ, Peterse JL, Mooi WJ, Wisman P, Lomans J, Dalesio O, Nusse R (1988) Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer. N Engl J Med 319:1239–1245
Weber K, Osborn M, Moll R, Wiklund B, Luening B (1984) Tissue polypeptide antigen (TPA) is related to the non-epidermal keratins 8, 18 and 19 typical of simple and non-squamous epithelia: reevaluation of a human tumor marker. EMBO J 3:2707–2714
Yamamoto T, Ikawa S, Akiyama T, Semba K, Nomura N, Muyajima N, Saito T, Toyoshima K (1986) Similarity of protein encoded by the human c-erbB-2 gene to epidermal growth factor receptor. Nature 319:230–234
Yokota J, Yamamoto T, Toyoshima K, Terada M, Sugimura T, Battifora H, Cline MJ (1986) Amplification of c-erbB-2 oncogene in human adenocarcinomas in vivo. Lancet 1:765–766
Zhou D, Battifora H, Yokota J, Yamamoto T, Cline MJ (1987) Association of multipole copies of the c-erbB-2 oncogene with spread of breast carcinoma. Cancer Research 47:6123–6125
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Brumm, C., Rivière, A., Wilckens, C. et al. Immunohistochemical investigation and Northern blot analysis of c-erbB-2 expression in normal, premalignant and malignant tissues of the corpus and cervix uteri. Vichows Archiv A Pathol Anat 417, 477–484 (1990). https://doi.org/10.1007/BF01625727
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DOI: https://doi.org/10.1007/BF01625727