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Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1994 Oct;47(10):914–919. doi: 10.1136/jcp.47.10.914

Expression of c-erbB-2, c-myc, and c-ras oncoproteins, insulin-like growth factor receptor I, and epidermal growth factor receptor in ovarian carcinoma.

P A van Dam 1, I B Vergote 1, D G Lowe 1, J V Watson 1, P van Damme 1, J C van der Auwera 1, J H Shepherd 1
PMCID: PMC502175  PMID: 7962604

Abstract

AIMS--To assess whether the overexpression of five dominant oncogene encoded proteins is crucial to the pathogenesis of ovarian carcinoma and whether this provides any useful prognostic information. METHODS--The expression of the insulin-like growth factor 1 receptor (ILGFR 1), epidermal growth factor receptor (EGFR), and the c-erbB-2, c-ras, and c-myc products was studied by multiparameter flow cytometry in 80 patients with epithelial ovarian cancer for whom long term follow up was available. RESULTS--Overexpression of ILGFR 1, EGFR, c-erbB-2, c-ras and c-myc was found in, respectively, nine of 80 (11%), 10 of 80 (12%), 19 of 80 (24%), 16 of 80 (20%) and 28 of 80 (35%) ovarian carcinomas. The levels of expression of ILGFR 1, EGFR, c-erbB-2 and c-ras were significantly higher in the tumours of patients with recurrent or persistent disease after chemotherapy than in the tumours of patients at initial presentation (p < 0.02). Multivariate analysis showed that residual tumour (p < 0.001), FIGO stage (p = 0.002), EGFR overexpression (p = 0.030) and previous chemotherapy (p = 0.034) were independent variables for predicting survival. CONCLUSIONS--Overexpression of these oncoproteins only occurs in a small proportion of ovarian carcinomas but may have an important role in the progression of the disease.

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Selected References

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  1. Bauknecht T., Birmelin G., Kommoss F. Clinical significance of oncogenes and growth factors in ovarian carcinomas. J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):855–862. doi: 10.1016/0960-0760(90)90432-k. [DOI] [PubMed] [Google Scholar]
  2. Bauknecht T., Janz I., Kohler M., Pfleiderer A. Human ovarian carcinomas: correlation of malignancy and survival with the expression of epidermal growth factor receptors (EGF-R) and EGF-like factors (EGF-F). Med Oncol Tumor Pharmacother. 1989;6(2):121–127. doi: 10.1007/BF02985234. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Berchuck A., Rodriguez G. C., Kamel A., Dodge R. K., Soper J. T., Clarke-Pearson D. L., Bast R. C., Jr Epidermal growth factor receptor expression in normal ovarian epithelium and ovarian cancer. I. Correlation of receptor expression with prognostic factors in patients with ovarian cancer. Am J Obstet Gynecol. 1991 Feb;164(2):669–674. doi: 10.1016/s0002-9378(11)80044-x. [DOI] [PubMed] [Google Scholar]
  5. Bos J. L. ras oncogenes in human cancer: a review. Cancer Res. 1989 Sep 1;49(17):4682–4689. [PubMed] [Google Scholar]
  6. Combaret V., Wang Q., Favrot M. C., Thiesse P., Philip I., Bouffet E., Bailly C., Bouvier R., Chauvin F., Zucker J. M. Clinical value of N-myc oncogene amplification in 52 patients with neuroblastoma included in recent therapeutic protocols. Eur J Cancer Clin Oncol. 1989 Nov;25(11):1607–1612. doi: 10.1016/0277-5379(89)90305-2. [DOI] [PubMed] [Google Scholar]
  7. Evan G. I., Lewis G. K., Ramsay G., Bishop J. M. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Mol Cell Biol. 1985 Dec;5(12):3610–3616. doi: 10.1128/mcb.5.12.3610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fukumoto M., Estensen R. D., Sha L., Oakley G. J., Twiggs L. B., Adcock L. L., Carson L. F., Roninson I. B. Association of Ki-ras with amplified DNA sequences, detected in human ovarian carcinomas by a modified in-gel renaturation assay. Cancer Res. 1989 Apr 1;49(7):1693–1697. [PubMed] [Google Scholar]
  9. Gullick W. J., Berger M. S., Bennett P. L., Rothbard J. B., Waterfield M. D. Expression of the c-erbB-2 protein in normal and transformed cells. Int J Cancer. 1987 Aug 15;40(2):246–254. doi: 10.1002/ijc.2910400221. [DOI] [PubMed] [Google Scholar]
  10. Gullick W. J., Marsden J. J., Whittle N., Ward B., Bobrow L., Waterfield M. D. Expression of epidermal growth factor receptors on human cervical, ovarian, and vulval carcinomas. Cancer Res. 1986 Jan;46(1):285–292. [PubMed] [Google Scholar]
  11. 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]
  12. Henzen-Logmans S. C., Berns E. M., Klijn J. G., van der Burg M. E., Foekens J. A. Epidermal growth factor receptor in ovarian tumours: correlation of immunohistochemistry with ligand binding assay. Br J Cancer. 1992 Dec;66(6):1015–1021. doi: 10.1038/bjc.1992.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kacinski B. M., Mayer A. G., King B. L., Carter D., Chambers S. K. NEU protein overexpression in benign, borderline, and malignant ovarian neoplasms. Gynecol Oncol. 1992 Mar;44(3):245–253. doi: 10.1016/0090-8258(92)90051-j. [DOI] [PubMed] [Google Scholar]
  14. Kaida S., Fujikawa T., Endou S., Inaba S., Nagayama Y., Sakato H., Yamazaki Y., Sano S., Tanaka N., Yamada H. [The changes of mRNAs of both c-myc and MDR1 in CML-bc tumor cells during the clinical course: a case report]. Rinsho Ketsueki. 1989 May;30(5):697–701. [PubMed] [Google Scholar]
  15. Kohler M., Janz I., Wintzer H. O., Wagner E., Bauknecht T. The expression of EGF receptors, EGF-like factors and c-myc in ovarian and cervical carcinomas and their potential clinical significance. Anticancer Res. 1989 Nov-Dec;9(6):1537–1547. [PubMed] [Google Scholar]
  16. Masuda H., Battifora H., Yokota J., Meltzer S., Cline M. J. Specificity of proto-oncogene amplification in human malignant diseases. Mol Biol Med. 1987 Aug;4(4):213–227. [PubMed] [Google Scholar]
  17. McKenna W. G., Weiss M. C., Endlich B., Ling C. C., Bakanauskas V. J., Kelsten M. L., Muschel R. J. Synergistic effect of the v-myc oncogene with H-ras on radioresistance. Cancer Res. 1990 Jan 1;50(1):97–102. [PubMed] [Google Scholar]
  18. Muschel R. J., McKenna W. G. Oncogenes and tumor progression. Anticancer Res. 1989 Sep-Oct;9(5):1395–1406. [PubMed] [Google Scholar]
  19. Owens O. J., Leake R. E. Epidermal growth factor receptor in normal ovaries and benign ovarian tumours. Eur J Obstet Gynecol Reprod Biol. 1992 Dec 28;47(3):229–233. doi: 10.1016/0028-2243(92)90156-s. [DOI] [PubMed] [Google Scholar]
  20. Polacarz S. V., Hey N. A., Stephenson T. J., Hill A. S. C-myc oncogene product P62c-myc in ovarian mucinous neoplasms: immunohistochemical study correlated with malignancy. J Clin Pathol. 1989 Feb;42(2):148–152. doi: 10.1136/jcp.42.2.148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Preisler H. D., Raza A., Larson R., LeBeau M., Browman G., Goldberg J., Grunwald H., Volger R., Verkh L., Singh P. Protooncogene expression and the clinical characteristics of acute nonlymphocytic leukemia: A Leukemia Intergroup pilot study. Blood. 1989 Jan;73(1):255–262. [PubMed] [Google Scholar]
  22. Press M. F., Cordon-Cardo C., Slamon D. J. Expression of the HER-2/neu proto-oncogene in normal human adult and fetal tissues. Oncogene. 1990 Jul;5(7):953–962. [PubMed] [Google Scholar]
  23. Price K. M., Cuthbertson A. S., Varndell I. M., Sheppard P. W. The production and characterisation of monoclonal antibodies to myc, c-erbB-2 and EFG-receptor using a synthetic peptide approach. Dev Biol Stand. 1990;71:23–31. [PubMed] [Google Scholar]
  24. Rimoldi D., Srikantan V., Wilson V. L., Bassin R. H., Samid D. Increased sensitivity of nontumorigenic fibroblasts expressing ras or myc oncogenes to malignant transformation induced by 5-aza-2'-deoxycytidine. Cancer Res. 1991 Jan 1;51(1):324–330. [PubMed] [Google Scholar]
  25. Rodenburg C. J., Koelma I. A., Nap M., Fleuren G. J. Immunohistochemical detection of the ras oncogene product p21 in advanced ovarian cancer. Lack of correlation with clinical outcome. Arch Pathol Lab Med. 1988 Feb;112(2):151–154. [PubMed] [Google Scholar]
  26. Ross D. W., Dent G. Juvenile chronic myeloid leukemia: oncogene characterization. Pediatr Pathol. 1989;9(6):669–678. doi: 10.3109/15513818909022374. [DOI] [PubMed] [Google Scholar]
  27. Sasano H., Garrett C. T., Wilkinson D. S., Silverberg S., Comerford J., Hyde J. Protooncogene amplification and tumor ploidy in human ovarian neoplasms. Hum Pathol. 1990 Apr;21(4):382–391. doi: 10.1016/0046-8177(90)90199-f. [DOI] [PubMed] [Google Scholar]
  28. Shepherd J. H. Revised FIGO staging for gynaecological cancer. Br J Obstet Gynaecol. 1989 Aug;96(8):889–892. doi: 10.1111/j.1471-0528.1989.tb03341.x. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Slamon D. J., deKernion J. B., Verma I. M., Cline M. J. Expression of cellular oncogenes in human malignancies. Science. 1984 Apr 20;224(4646):256–262. doi: 10.1126/science.6538699. [DOI] [PubMed] [Google Scholar]
  31. Tsujino T., Yoshida K., Nakayama H., Ito H., Shimosato T., Tahara E. Alterations of oncogenes in metastatic tumours of human gastric carcinomas. Br J Cancer. 1990 Aug;62(2):226–230. doi: 10.1038/bjc.1990.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Vogelstein B. Cancer. A deadly inheritance. Nature. 1990 Dec 20;348(6303):681–682. doi: 10.1038/348681a0. [DOI] [PubMed] [Google Scholar]
  33. Waterfield M. D., Mayes E. L., Stroobant P., Bennet P. L., Young S., Goodfellow P. N., Banting G. S., Ozanne B. A monoclonal antibody to the human epidermal growth factor receptor. J Cell Biochem. 1982;20(2):149–161. doi: 10.1002/jcb.240200207. [DOI] [PubMed] [Google Scholar]
  34. Watson J. V., Curling O. M., Munn C. F., Hudson C. N. Oncogene expression in ovarian cancer: a pilot study of c-myc oncoprotein in serous papillary ovarian cancer. Gynecol Oncol. 1987 Oct;28(2):137–150. doi: 10.1016/0090-8258(87)90207-1. [DOI] [PubMed] [Google Scholar]
  35. Weinstein I. B. The origins of human cancer: molecular mechanisms of carcinogenesis and their implications for cancer prevention and treatment--twenty-seventh G.H.A. Clowes memorial award lecture. Cancer Res. 1988 Aug 1;48(15):4135–4143. [PubMed] [Google Scholar]
  36. Yaginuma Y., Yamashita K., Kuzumaki N., Fujita M., Shimizu T. ras oncogene product p21 expression and prognosis of human ovarian tumors. Gynecol Oncol. 1992 Jul;46(1):45–50. doi: 10.1016/0090-8258(92)90194-n. [DOI] [PubMed] [Google Scholar]
  37. van 't Veer L. J., Hermens R., van den Berg-Bakker L. A., Cheng N. C., Fleuren G. J., Bos J. L., Cleton F. J., Schrier P. I. ras oncogene activation in human ovarian carcinoma. Oncogene. 1988 Feb;2(2):157–165. [PubMed] [Google Scholar]
  38. van Dam P. A., Lowe D. G., Shepherd J. H., Vergote I. B., Watson J. V. Multiparameter flow cytometric quantification of membrane proteins in long-term cryopreserved tissue blocks. Lancet. 1990 Sep 15;336(8716):689–689. doi: 10.1016/0140-6736(90)92183-i. [DOI] [PubMed] [Google Scholar]
  39. van Dam P. A., Lowe D. G., Watson J. V., James M., Chard T., Hudson C. N., Shepherd J. H. Multiparameter flow-cytometric quantitation of epidermal growth factor receptor and c-erbB-2 oncoprotein in normal and neoplastic tissues of the female genital tract. Gynecol Oncol. 1991 Sep;42(3):256–264. doi: 10.1016/0090-8258(91)90355-9. [DOI] [PubMed] [Google Scholar]
  40. van Dam P. A., Watson J. V., Lowe D. G., Chard T., Shepherd J. H. Comparative evaluation of fresh, fixed, and cryopreserved solid tumor cells for reliable flow cytometry of DNA and tumor associated antigen. Cytometry. 1992;13(7):722–729. doi: 10.1002/cyto.990130708. [DOI] [PubMed] [Google Scholar]
  41. van Dam P. A., Watson J. V., Lowe D. G., Cox H., Curling M., Shepherd J. H. Tissue preparation for simultaneous flow cytometric quantitation of tumour associated antigens and DNA in solid tumours. J Clin Pathol. 1990 Oct;43(10):833–839. doi: 10.1136/jcp.43.10.833. [DOI] [PMC free article] [PubMed] [Google Scholar]

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