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Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma
Y Ito, T Takeda, M Sakon and 6 more
British Journal of Cancer · 2001
Abstract
In order to elucidate the clinical significance of the erbB family, epidermal growth factor receptor (EGF-R), c-erbB-2, c-erbB-3 and c-erbB-4 in hepatocellular carcinoma (HCC), we investigated the expression of these proteins by means of immunohistochemistry for HCC as well as adjacent noncancerous lesions. EGF-R was expressed in 68% of the HCC examined and showed correlation with the proliferating activity, stage, intrahepatic metastasis and carcinoma differentiation. c-erbB-2 was expressed in only 21% of the cases and showed no relationships with the clinicopathological parameters. c-erbB-3 protein was observed in 84% of the HCC and 38.1% of the noncancerous lesions. Its expression in HCC was equal to or greater than noncancerous lesions in 90.5% of the cases, and was related to the stage, portal invasion, cell proliferating activity, tumour size, intrahepatic metastasis and carcinoma differentiation. c-erbB-4 protein was expressed in 61.0% of HCC and in as much as 86.1% of the noncancerous lesions. Unlike the expression of c-erbB-3, that of c-erbB-4 in HCC was less than that of the adjacent noncancerous lesions in 51.2% of the cases. No statistical significance could be established between this protein expression in HCC and clinicopathological features. EGF-R and c-erbB-3 affected disease-free survival, but were not recognized as independent prognostic factors by multivariate analysis. The present study suggests that, of the four receptors, EGF-R and c-erbB-3 play important roles in the progression of HCC.
References 49
- 1.
Bacus S. S., Chin D., Yarden Y., Zelnick C. R., Stern D. F. Type 1 receptor tyrosine kinases are differentially phosphorylated in mammary carcinoma and differentially associated with steroid receptors. Am J Pathol. 1996;148(2):549-558.
Not in our library
- 2.
Baulida J., Kraus M. H., Alimandi M., Di Fiore P. P., Carpenter G. All ErbB receptors other than the epidermal growth factor receptor are endocytosis impaired. J Biol Chem. 1996;271(9):5251-5257.
Not in our library10.1074/jbc.271.9.5251
- 3.
Beasley R. P., Hwang L. Y., Lin C. C., Chien C. S. Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet. 1981;2(8256):1129-1133.
Not in our library10.1016/s0140-6736(81)90585-7
- 4.
Berchuck A., Kamel A., Whitaker R., Kerns B., Olt G., Kinney R., Soper J. T., Dodge R., Clarke-Pearson D. L., Marks P. Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res. 1990;50(13):4087-4091.
Not in our library
- 5.
Bobrow L. G., Millis R. R., Happerfield L. C., Gullick W. J. c-erbB-3 protein expression in ductal carcinoma in situ of the breast. Eur J Cancer. 1997;33(11):1846-1850.
Not in our library10.1016/s0959-8049(97)00244-x
- 6.
Bodey B., Bodey B., Gröger A. M., Luck J. V., Siegel S. E., Taylor C. R., Kaiser H. E. Clinical and prognostic significance of the expression of the c-erbB-2 and c-erbB-3 oncoproteins in primary and metastatic malignant melanomas and breast carcinomas. Anticancer Res. 1997;17(2B):1319-1330.
Not in our library
- 7.
Borg A., Tandon A. K., Sigurdsson H., Clark G. M., Fernö M., Fuqua S. A., Killander D., McGuire W. L. HER-2/neu amplification predicts poor survival in node-positive breast cancer. Cancer Res. 1990;50(14):4332-4337.
Not in our library
- 8.
Brunt E. M., Swanson P. E. Immunoreactivity for c-erbB-2 oncopeptide in benign and malignant diseases of the liver. Am J Clin Pathol. 1992;97(5 Suppl 1):S53-S61.
Not in our library
- 9.
Cantley L. C., Auger K. R., Carpenter C., Duckworth B., Graziani A., Kapeller R., Soltoff S. Oncogenes and signal transduction. Cell. 1991;64(2):281-302.
Not in our library10.1016/0092-8674(91)90639-g
- 10.
Chang C. P., Lazar C. S., Walsh B. J., Komuro M., Collawn J. F., Kuhn L. A., Tainer J. A., Trowbridge I. S., Farquhar M. G., Rosenfeld M. G. Ligand-induced internalization of the epidermal growth factor receptor is mediated by multiple endocytic codes analogous to the tyrosine motif found in constitutively internalized receptors. J Biol Chem. 1993;268(26):19312-19320.
Not in our library
- 11.
Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162(1):156-159.
Not in our library10.1006/abio.1987.9999
- 12.
Chow N. H., Liu H. S., Yang H. B., Chan S. H., Su I. J. Expression patterns of erbB receptor family in normal urothelium and transitional cell carcinoma. An immunohistochemical study. Virchows Arch. 1997;430(6):461-466.
Not in our library10.1007/s004280050056
- 13.
Collier J. D., Guo K., Mathew J., May F. E., Bennett M. K., Corbett I. P., Bassendine M. F., Burt A. D. c-erbB-2 oncogene expression in hepatocellular carcinoma and cholangiocarcinoma. J Hepatol. 1992;14(2-3):377-380.
Not in our library10.1016/0168-8278(92)90186-s
- 14.
Dugan M. C., Dergham S. T., Kucway R., Singh K., Biernat L., Du W., Vaitkevicius V. K., Crissman J. D., Sarkar F. H. HER-2/neu expression in pancreatic adenocarcinoma: relation to tumor differentiation and survival. Pancreas. 1997;14(3):229-236.
Not in our library10.1097/00006676-199704000-00003
- 15.
Elenius K., Paul S., Allison G., Sun J., Klagsbrun M. Activation of HER4 by heparin-binding EGF-like growth factor stimulates chemotaxis but not proliferation. EMBO J. 1997;16(6):1268-1278.
Not in our library10.1093/emboj/16.6.1268
- 16.
Friess H., Fukuda A., Tang W. H., Eichenberger A., Furlan N., Zimmermann A., Korc M., Büchler M. W. Concomitant analysis of the epidermal growth factor receptor family in esophageal cancer: overexpression of epidermal growth factor receptor mRNA but not of c-erbB-2 and c-erbB-3. World J Surg. 1999;23(10):1010-1018.
Not in our library10.1007/s002689900616
- 17.
Haugen D. R., Akslen L. A., Varhaug J. E., Lillehaug J. R. Expression of c-erbB-3 and c-erbB-4 proteins in papillary thyroid carcinomas. Cancer Res. 1996;56(6):1184-1188.
Not in our library
- 18.
Häussler O., Epstein J. I., Amin M. B., Heitz P. U., Hailemariam S. Cell proliferation, apoptosis, oncogene, and tumor suppressor gene status in adenosis with comparison to benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and cancer. Hum Pathol. 1999;30(9):1077-1086.
Not in our library10.1016/s0046-8177(99)90226-5
- 19.
Ibrahim S. O., Vasstrand E. N., Liavaag P. G., Johannessen A. C., Lillehaug J. R. Expression of c-erbB proto-oncogene family members in squamous cell carcinoma of the head and neck. Anticancer Res. 1997;17(6D):4539-4546.
Not in our library
- 20.
Ito Y., Matsuura N., Sakon M., Takeda T., Umeshita K., Nagano H., Nakamori S., Dono K., Tsujimoto M., Nakahara M. Both cell proliferation and apoptosis significantly predict shortened disease-free survival in hepatocellular carcinoma. Br J Cancer. 1999;81(4):747-751.
Not in our library10.1038/sj.bjc.6690758
- 21.
Kameda T., Yasui W., Yoshida K., Tsujino T., Nakayama H., Ito M., Ito H., Tahara E. Expression of ERBB2 in human gastric carcinomas: relationship between p185ERBB2 expression and the gene amplification. Cancer Res. 1990;50(24):8002-8009.
Not in our library
- 22.
Kapitanović S., Radosević S., Slade N., Kapitanović M., Andelinović S., Ferencić Z., Tavassoli M., Spaventi S., Pavelić K., Spaventi R. Expression of erbB-3 protein in colorectal adenocarcinoma: correlation with poor survival. J Cancer Res Clin Oncol. 2000;126(4):205-211.
Not in our library10.1007/s004320050034
- 23.
Kern J. A., Schwartz D. A., Nordberg J. E., Weiner D. B., Greene M. I., Torney L., Robinson R. A. p185neu expression in human lung adenocarcinomas predicts shortened survival. Cancer Res. 1990;50(16):5184-5187.
Not in our library
- 24.
Kew T. Y., Bell J. A., Pinder S. E., Denley H., Srinivasan R., Gullick W. J., Nicholson R. I., Blamey R. W., Ellis I. O. c-erbB-4 protein expression in human breast cancer. Br J Cancer. 2000;82(6):1163-1170.
Not in our library10.1054/bjoc.1999.1057
- 25.
Kim H. H., Sierke S. L., Koland J. G. Epidermal growth factor-dependent association of phosphatidylinositol 3-kinase with the erbB3 gene product. J Biol Chem. 1994;269(40):24747-24755.
Not in our library
- 26.
Kira S., Nakanishi T., Suemori S., Kitamoto M., Watanabe Y., Kajiyama G. Expression of transforming growth factor alpha and epidermal growth factor receptor in human hepatocellular carcinoma. Liver. 1997;17(4):177-182.
Not in our library10.1111/j.1600-0676.1997.tb00803.x
- 27.
Komurasaki T., Toyoda H., Uchida D., Morimoto S. Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4. Oncogene. 1997;15(23):2841-2848.
Not in our library10.1038/sj.onc.1201458
- 28.
Kraus M. H., Issing W., Miki T., Popescu N. C., Aaronson S. A. Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors. Proc Natl Acad Sci U S A. 1989;86(23):9193-9197.
Not in our library10.1073/pnas.86.23.9193
- 29.
Lee C. S., Pirdas A. Epidermal growth factor receptor immunoreactivity in gallbladder and extrahepatic biliary tract tumours. Pathol Res Pract. 1995;191(11):1087-1091.
Not in our library10.1016/s0344-0338(11)80652-7
- 30.
Nakopoulou L., Stefanaki K., Filaktopoulos D., Giannopoulou I. C-erb-B-2 oncoprotein and epidermal growth factor receptor in human hepatocellular carcinoma: an immunohistochemical study. Histol Histopathol. 1994;9(4):677-682.
Not in our library
- 31.
Pinkas-Kramarski R., Soussan L., Waterman H., Levkowitz G., Alroy I., Klapper L., Lavi S., Seger R., Ratzkin B. J., Sela M. Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions. EMBO J. 1996;15(10):2452-2467.
Not in our library
- 32.
Plowman G. D., Culouscou J. M., Whitney G. S., Green J. M., Carlton G. W., Foy L., Neubauer M. G., Shoyab M. Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family. Proc Natl Acad Sci U S A. 1993;90(5):1746-1750.
Not in our library10.1073/pnas.90.5.1746
- 33.
Riese D. J., Bermingham Y., van Raaij T. M., Buckley S., Plowman G. D., Stern D. F. Betacellulin activates the epidermal growth factor receptor and erbB-4, and induces cellular response patterns distinct from those stimulated by epidermal growth factor or neuregulin-beta. Oncogene. 1996;12(2):345-353.
Not in our library
- 34.
Saito I., Miyamura T., Ohbayashi A., Harada H., Katayama T., Kikuchi S., Watanabe Y., Koi S., Onji M., Ohta Y. Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc Natl Acad Sci U S A. 1990;87(17):6547-6549.
Not in our library10.1073/pnas.87.17.6547
- 35.
Sanidas E. E., Filipe M. I., Linehan J., Lemoine N. R., Gullick W. J., Rajkumar T., Levison D. A. Expression of the c-erbB-3 gene product in gastric cancer. Int J Cancer. 1993;54(6):935-940.
Not in our library10.1002/ijc.2910540612
- 36.
Sasaki K., Murakami T., Kawasaki M., Takahashi M. The cell cycle associated change of the Ki-67 reactive nuclear antigen expression. J Cell Physiol. 1987;133(3):579-584.
Not in our library10.1002/jcp.1041330321
- 37.
Shintani S., Funayama T., Yoshihama Y., Alcalde R. E., Ootsuki K., Terakado N., Matsumura T. Expression of c-erbB family gene products in adenoid cystic carcinoma of salivary glands: an immunohistochemical study. Anticancer Res. 1995;15(6B):2623-2626.
Not in our library
- 38.
Simpson B. J., Phillips H. A., Lessells A. M., Langdon S. P., Miller W. R. c-erbB growth-factor-receptor proteins in ovarian tumours. Int J Cancer. 1995;64(3):202-206.
Not in our library10.1002/ijc.2910640310
- 39.
Soltoff S. P., Carraway K. L., Prigent S. A., Gullick W. G., Cantley L. C. ErbB3 is involved in activation of phosphatidylinositol 3-kinase by epidermal growth factor. Mol Cell Biol. 1994;14(6):3550-3558.
Not in our library10.1128/mcb.14.6.3550-3558.1994
- 40.
Srinivasan R., Benton E., McCormick F., Thomas H., Gullick W. J. Expression of the c-erbB-3/HER-3 and c-erbB-4/HER-4 growth factor receptors and their ligands, neuregulin-1 alpha, neuregulin-1 beta, and betacellulin, in normal endometrium and endometrial cancer. Clin Cancer Res. 1999;5(10):2877-2883.
Not in our library
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