Abstract
Aims—To study the prevalence of overexpression of c-erbB3 growth factor receptor in ovarian carcinomas and to analyse its relation to histological subtype, stage and grade of the tumours.
Methods—Ninety eight ovarian carcinomas were evaluated immunohistochemically using the RTJ1 monoclonal antibody raised against a synthetic peptide, the sequence of which was derived from the cytoplasmic domain of the c-erbB3 protein.
Results—Of the tumours, 16% (16/98) overexpressed c-erbB3 protein relative to normal ovarian epithelium, whereas 22% (22/98) were completely negative. There was a statistically significant association between overexpression and well differentiated grade.
Conclusions—These findings suggest that c-erbB3 protein overexpression occurs in a significant proportion of ovarian cancers and is correlated with differentiation. Overexpression may merit further investigation as a potential prognostic indicator and as a target for new treatment.
Keywords: c-erbB3 protein
Keywords: overexpression
Keywords: ovarian cancer
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- Alimandi M., Romano A., Curia M. C., Muraro R., Fedi P., Aaronson S. A., Di Fiore P. P., Kraus M. H. Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene. 1995 May 4;10(9):1813–1821. [PubMed] [Google Scholar]
- Baselga J., Norton L., Masui H., Pandiella A., Coplan K., Miller W. H., Jr, Mendelsohn J. Antitumor effects of doxorubicin in combination with anti-epidermal growth factor receptor monoclonal antibodies. J Natl Cancer Inst. 1993 Aug 18;85(16):1327–1333. doi: 10.1093/jnci/85.16.1327. [DOI] [PubMed] [Google Scholar]
- Beerli R. R., Graus-Porta D., Woods-Cook K., Chen X., Yarden Y., Hynes N. E. Neu differentiation factor activation of ErbB-3 and ErbB-4 is cell specific and displays a differential requirement for ErbB-2. Mol Cell Biol. 1995 Dec;15(12):6496–6505. doi: 10.1128/mcb.15.12.6496. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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 Jul 1;50(13):4087–4091. [PubMed] [Google Scholar]
- Carraway K. L., 3rd, Sliwkowski M. X., Akita R., Platko J. V., Guy P. M., Nuijens A., Diamonti A. J., Vandlen R. L., Cantley L. C., Cerione R. A. The erbB3 gene product is a receptor for heregulin. J Biol Chem. 1994 May 13;269(19):14303–14306. [PubMed] [Google Scholar]
- Fan Z., Baselga J., Masui H., Mendelsohn J. Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established A431 cell xenografts. Cancer Res. 1993 Oct 1;53(19):4637–4642. [PubMed] [Google Scholar]
- Foulkes W. D., Ragoussis J., Stamp G. W., Allan G. J., Trowsdale J. Frequent loss of heterozygosity on chromosome 6 in human ovarian carcinoma. Br J Cancer. 1993 Mar;67(3):551–559. doi: 10.1038/bjc.1993.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gasparini G., Gullick W. J., Maluta S., Dalla Palma P., Caffo O., Leonardi E., Boracchi P., Pozza F., Lemoine N. R., Bevilacqua P. c-erbB-3 and c-erbB-2 protein expression in node-negative breast carcinoma--an immunocytochemical study. Eur J Cancer. 1994;30A(1):16–22. doi: 10.1016/s0959-8049(05)80010-3. [DOI] [PubMed] [Google Scholar]
- Guy P. M., Platko J. V., Cantley L. C., Cerione R. A., Carraway K. L., 3rd Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase activity. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8132–8136. doi: 10.1073/pnas.91.17.8132. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haldane J. S., Hird V., Hughes C. M., Gullick W. J. c-erbB-2 oncogene expression in ovarian cancer. J Pathol. 1990 Nov;162(3):231–237. doi: 10.1002/path.1711620309. [DOI] [PubMed] [Google Scholar]
- Hunt C.R., Hale R.J., Armstrong C., Rajkumar T., Gullick W.J., Buckley C.H. c-erbB-3 proto-oncogene expression in uterine cervical carcinoma. Int J Gynecol Cancer. 1995 Jul;5(4):282–285. doi: 10.1046/j.1525-1438.1995.05040282.x. [DOI] [PubMed] [Google Scholar]
- Issing W. J., Heppt W. J., Kastenbauer E. R. erbB-3, a third member of the erbB/epidermal growth factor receptor gene family: its expression in head and neck cancer cell lines. Eur Arch Otorhinolaryngol. 1993;250(7):392–395. doi: 10.1007/BF00180383. [DOI] [PubMed] [Google Scholar]
- Katoh M., Yazaki Y., Sugimura T., Terada M. c-erbB3 gene encodes secreted as well as transmembrane receptor tyrosine kinase. Biochem Biophys Res Commun. 1993 May 14;192(3):1189–1197. doi: 10.1006/bbrc.1993.1542. [DOI] [PubMed] [Google Scholar]
- Kita Y. A., Barff J., Luo Y., Wen D., Brankow D., Hu S., Liu N., Prigent S. A., Gullick W. J., Nicolson M. NDF/heregulin stimulates the phosphorylation of Her3/erbB3. FEBS Lett. 1994 Jul 25;349(1):139–143. doi: 10.1016/0014-5793(94)00644-x. [DOI] [PubMed] [Google Scholar]
- 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 Dec;86(23):9193–9197. doi: 10.1073/pnas.86.23.9193. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leary J. A., Edwards B. G., Houghton C. R., Kefford R. F., Friedlander M. L. Amplification of HER-2/neu oncogene in human ovarian cancer. Int J Gynecol Cancer. 1992 Nov;2(6):291–294. doi: 10.1046/j.1525-1438.1992.02060291.x. [DOI] [PubMed] [Google Scholar]
- Lemoine N. R., Barnes D. M., Hollywood D. P., Hughes C. M., Smith P., Dublin E., Prigent S. A., Gullick W. J., Hurst H. C. Expression of the ERBB3 gene product in breast cancer. Br J Cancer. 1992 Dec;66(6):1116–1121. doi: 10.1038/bjc.1992.420. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lemoine N. R., Lobresco M., Leung H., Barton C., Hughes C. M., Prigent S. A., Gullick W. J., Klöppel G. The erbB-3 gene in human pancreatic cancer. J Pathol. 1992 Nov;168(3):269–273. doi: 10.1002/path.1711680305. [DOI] [PubMed] [Google Scholar]
- Mandai M., Konishi I., Koshiyama M., Mori T., Arao S., Tashiro H., Okamura H., Nomura H., Hiai H., Fukumoto M. Expression of metastasis-related nm23-H1 and nm23-H2 genes in ovarian carcinomas: correlation with clinicopathology, EGFR, c-erbB-2, and c-erbB-3 genes, and sex steroid receptor expression. Cancer Res. 1994 Apr 1;54(7):1825–1830. [PubMed] [Google Scholar]
- Myers R. B., Srivastava S., Oelschlager D. K., Grizzle W. E. Expression of p160erbB-3 and p185erbB-2 in prostatic intraepithelial neoplasia and prostatic adenocarcinoma. J Natl Cancer Inst. 1994 Aug 3;86(15):1140–1145. doi: 10.1093/jnci/86.15.1140. [DOI] [PubMed] [Google Scholar]
- Plowman G. D., Green J. M., Culouscou J. M., Carlton G. W., Rothwell V. M., Buckley S. Heregulin induces tyrosine phosphorylation of HER4/p180erbB4. Nature. 1993 Dec 2;366(6454):473–475. doi: 10.1038/366473a0. [DOI] [PubMed] [Google Scholar]
- Prigent S. A., Lemoine N. R., Hughes C. M., Plowman G. D., Selden C., Gullick W. J. Expression of the c-erbB-3 protein in normal human adult and fetal tissues. Oncogene. 1992 Jul;7(7):1273–1278. [PubMed] [Google Scholar]
- Quinn C. M., Ostrowski J. L., Lane S. A., Loney D. P., Teasdale J., Benson F. A. c-erbB-3 protein expression in human breast cancer: comparison with other tumour variables and survival. Histopathology. 1994 Sep;25(3):247–252. doi: 10.1111/j.1365-2559.1994.tb01324.x. [DOI] [PubMed] [Google Scholar]
- Rajkumar T., Gooden C. S., Lemoine N. R., Gullick W. J., Goden C. S. Expression of the c-erbB-3 protein in gastrointestinal tract tumours determined by monoclonal antibody RTJ1. J Pathol. 1993 Jul;170(3):271–278. doi: 10.1002/path.1711700309. [DOI] [PubMed] [Google Scholar]
- Rajkumar T., Gullick W. J. A monoclonal antibody to the human c-erbB3 protein stimulates the anchorage-independent growth of breast cancer cell lines. Br J Cancer. 1994 Sep;70(3):459–465. doi: 10.1038/bjc.1994.328. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Riese D. J., 2nd, van Raaij T. M., Plowman G. D., Andrews G. C., Stern D. F. The cellular response to neuregulins is governed by complex interactions of the erbB receptor family. Mol Cell Biol. 1995 Oct;15(10):5770–5776. doi: 10.1128/mcb.15.10.5770. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rubin S. C., Finstad C. L., Wong G. Y., Almadrones L., Plante M., Lloyd K. O. Prognostic significance of HER-2/neu expression in advanced epithelial ovarian cancer: a multivariate analysis. Am J Obstet Gynecol. 1993 Jan;168(1 Pt 1):162–169. doi: 10.1016/s0002-9378(12)90907-2. [DOI] [PubMed] [Google Scholar]
- Salomon D. S., Brandt R., Ciardiello F., Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. 1995 Jul;19(3):183–232. doi: 10.1016/1040-8428(94)00144-i. [DOI] [PubMed] [Google Scholar]
- 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 Jul 30;54(6):935–940. doi: 10.1002/ijc.2910540612. [DOI] [PubMed] [Google Scholar]
- Scambia G., Benedetti Panici P., Battaglia F., Ferrandina G., Baiocchi G., Greggi S., De Vincenzo R., Mancuso S. Significance of epidermal growth factor receptor in advanced ovarian cancer. J Clin Oncol. 1992 Apr;10(4):529–535. doi: 10.1200/JCO.1992.10.4.529. [DOI] [PubMed] [Google Scholar]
- Simpson B. J., Weatherill J., Miller E. P., Lessells A. M., Langdon S. P., Miller W. R. c-erbB-3 protein expression in ovarian tumours. Br J Cancer. 1995 Apr;71(4):758–762. doi: 10.1038/bjc.1995.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Singleton T. P., Perrone T., Oakley G., Niehans G. A., Carson L., Cha S. S., Strickler J. G. Activation of c-erbB-2 and prognosis in ovarian carcinoma. Comparison with histologic type, grade, and stage. Cancer. 1994 Mar 1;73(5):1460–1466. doi: 10.1002/1097-0142(19940301)73:5<1460::aid-cncr2820730523>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
- Slamon D. J., Godolphin W., Jones L. A., Holt J. A., Wong S. G., Keith D. E., Levin W. J., Stuart S. G., Udove J., Ullrich A. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989 May 12;244(4905):707–712. doi: 10.1126/science.2470152. [DOI] [PubMed] [Google Scholar]