Skip to main content
NCBI home page
Journal of Cancer Research and Clinical Oncology logoLink to Journal of Cancer Research and Clinical Oncology
. 1994 Dec;120(12):737–742. doi: 10.1007/BF01194273

Coexpression of HER-2/neu and p53 is associated with a shorter disease-free survival in node-positive breast cancer patients

C Wiltschke 1,✉, I Kindas-Muegge 2, A Steininger 1, A Reiner 3, G Reiner 4, P N Preis 5
PMCID: PMC12201898  PMID: 7798300

Abstract

Breast cancer tissue was examined for overexpression of HER-2/neu and p53 oncogene proteins. Samples from 105 breast cancer patients were investigated by Western-blot analysis and their relationship to other established markers and clinical outcome was examined. In 21.0% of the cases HER-2/neu was overexpressed, and in 46.7% the p53 protein level was increased. Expression of these two oncogene products was closely correlated. Overexpression of both oncogenes was associated with larger tumour size and negative hormone receptor. The percentage of HER-2/neu and p53 overexpression was higher in node-positive patients, although statistical evaluation was not significant. While overexpression of HER-2/neu as well as p53 in node-positive patients was associated insignificantly with shorter disease-free survival, a significant difference could be documented when the disease-free survival of patients with overexpression of both oncogene proteins was compared to that of patients with no overexpression.

Key words: HER-2/neu, p53, Breast cancer

References

  1. Aaltomaa S, Lipponen P, Eskelinen M, Kosma VM, Marin S, Alhava E, Syrjanen K (1993) Comparison of classic and quantitative prognostic factors in hormone receptor-positive and hormone receptor-negative female breast cancer. Am J Surg 165:307–311 [DOI] [PubMed] [Google Scholar]
  2. Allred DC, Clark GM, Elledge R, Fuqua SA, Brown RW, Chamness GC, Osborne CK, McGuire WL (1993) Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J Natl Cancer Inst 85:200–206 [DOI] [PubMed] [Google Scholar]
  3. Bargmann CI, Hung MC, Weinberg RA (1986) Multiple independent activations of theneu oncogene by a point mutation altering the transmembrane domain of p185. Cell 45:649–657 [DOI] [PubMed] [Google Scholar]
  4. Bishop JM (1987) The molecular genetics of cancer (review). Science 235:305–311 [DOI] [PubMed] [Google Scholar]
  5. Chang K, Ding I, Kern FG, Willingham MC (1991) Immunohistochemical analysis of p53 and HER-2/neu proteins in human tumors. J Histochem Cytochem 39:1281–1287 [DOI] [PubMed] [Google Scholar]
  6. Clark GM (1992) Integrating prognostic factors. Breast Cancer Res Treat 22:187–191 [DOI] [PubMed] [Google Scholar]
  7. Clark GM, McGuire WL (1991) Follow-up study of HER-2/neu amplification in primary breast cancer (review). Cancer Res 51:944–948 [PubMed] [Google Scholar]
  8. Contesso G, Jotti GS, Bonadonna G (1989) Tumor grade as a prognostic factor in primary breast cancer (review). Eur J Cancer Clin Oncol 25:403–409 [DOI] [PubMed] [Google Scholar]
  9. Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A, McGrath J, Seeburg PH, Libermann TA, Schlessinger J, Francke U, et al (1985) Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 230:1132–1139 [DOI] [PubMed] [Google Scholar]
  10. Crawford LV, Pim DC, Lamb P (1984) The cellular protein p53 in human tumors. Mol Biol Med 2:261–272 [PubMed] [Google Scholar]
  11. Davidoff AM, Herndon JE, Glover NS, Kerns BJ, Pence JC, Iglehart JD, Marks JR (1991) Relation between p53 overexpression and established prognostic factors in breast cancer. Surgery 110:259–264 [PubMed] [Google Scholar]
  12. Eliyahu D, Michalovitz D, Oren M (1985) Overproduction of p53 antigen makes established cells highly tumorigenic. Nature 316:158–160 [DOI] [PubMed] [Google Scholar]
  13. Elledge RM, Fuqua SA, Clark GM, Pujol P, Allred DC, McGuire WL (1993) Prognostic significance of p53 gene alterations in node-negative breast cancer. Breast Cancer Res Treat 26:225–235 [DOI] [PubMed] [Google Scholar]
  14. Finlay CA, Hinds PW, Levine AJ (1989) The p53 proto-oncogene can act as a suppressor of transformation. Cell 57:1083–1093 [DOI] [PubMed] [Google Scholar]
  15. Gannon JV, Greaves R, Iggo R, Lane DP (1990) Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form. EMBO J 9:1595–1602 [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gusterson BA, Gelber RD, Goldhirsch A, Price KN, Save-Soderborgh J, Anbazhagan R, Styles J, Rudenstam CM, Golouh R, Reed R, et al [International (Ludwig) Breast Cancer Study Group] (1992) Prognostic importance of c-erbB-2 expression in breast cancer. J Clin Oncol 10:1049–1056 [DOI] [PubMed] [Google Scholar]
  17. Harris CC, Hollstein M (1993) Clinical implications of the p53 tumor-suppressor gene (review). N Engl J Med 329:1318–1327 [DOI] [PubMed] [Google Scholar]
  18. Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations is human cancers (review). Science 253:49–53 [DOI] [PubMed] [Google Scholar]
  19. Ji H, Lipponen P, Aaltomaa S, Syrjanen S, Syrjanen K (1993) c-erbB-2 oncogene related to p53 expression, cell proliferation and prognosis in breast cancer. Anticancer Res 13:1147–1152 [PubMed] [Google Scholar]
  20. Kerns BJ, Jordan PA, Huper G, Marks JR, Iglehart JD, Layfied LJ (1993) Assessment of c-erbB-2 amplification by immunohistochemistry in paraffin-embedded breast cancer. Mod Pathol 6:673–678 [PubMed] [Google Scholar]
  21. King CR, Kraus MH, Aaronson SA (1985) Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science 229:974–976 [DOI] [PubMed] [Google Scholar]
  22. Lane DP, Crawford LV (1979) T antigen is bound to a host protein in SV40-transformed cells. Nature 278:261–263 [DOI] [PubMed] [Google Scholar]
  23. Linzer DI, Levine AJ (1979) Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell 17:43–52 [DOI] [PubMed] [Google Scholar]
  24. Mantel N (1966) Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50:163–170 [PubMed] [Google Scholar]
  25. Molina R, Ciocca DR, Tandon AK, Allred DC, Clark GM, Chamness GC, Gullick WJ, McGuire WL (1992) Expression of HER-2/neu oncoprotein in human breast cancer: a comparison of immunohistochemical and western blot techniques. Anticancer Res 12:1965–1971 [PubMed] [Google Scholar]
  26. Parada LF, Land H, Weinberg RA, Wolf D, Rotter V (1984) Cooperation between gene encoding p53 tumour antigen and ras in cellular transformation. Nature 312:649–651 [DOI] [PubMed] [Google Scholar]
  27. Pinhasi-Kimhi O, Michalovitz D, Ben-Zeev A, Oren M (1986) Specific interaction between the p53 cellular tumour antigen and major heat shock proteins. Nature 320:182–184 [DOI] [PubMed] [Google Scholar]
  28. Semba K, Kamata N, Toyoshima K, Yamamoto T (1985) A v-erbB-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. Proc Natl Acad Sci USA 82:6497–6501 [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Silvestrini R, Benini E, Daidone MG, Veneroni S, Boracchi P, Cappelletti V, Di Fronzo G, Veronesi U (1993) p53 as an independent prognostic marker in lymph node-negative breast cancer patients. J Natl Cancer Inst 85:965–970 [DOI] [PubMed] [Google Scholar]
  30. 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 235:177–182 [DOI] [PubMed] [Google Scholar]
  31. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC (1985) Measurement of protein using bicinchoninic acid [published erratum appears in Anal Biochem (1987) 163:279]. Anal Biochem 150:76–85 [DOI] [PubMed] [Google Scholar]
  32. Tainsky MA, Bischoff F, Strong LC (1992) A dual role for p53 in the progression of human cells toward cancer. Proc Am Assoc Cancer Res 33:2274 [Google Scholar]
  33. Tandon AK, Clark GM, Chamness GC, Ullrich A, McGuire WL (1989) HER-2/neu oncogene protein and prognosis in breast cancer. J Clin Oncol 7:1120–1128 [DOI] [PubMed] [Google Scholar]
  34. Thor AD, Moore DH,II, Edgerton SM, Kawasaki ES, Reihsaus E, Lynch HT, Marcus JN, Schwartz L, Chen LC, Mayall BH, et al (1992) Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers. J Natl Cancer Inst 84:845–855 [DOI] [PubMed] [Google Scholar]
  35. Toikkanen S, Helin H, Isola J, Joensuu H (1992) Prognostic significance of HER-2 oncoprotein expression in breast cancer: a 30-year follow-up. J Clin Oncol 10:1044–1048 [DOI] [PubMed] [Google Scholar]
  36. Venter DJ, Tuzi NL, Kumar S, Gullick WJ (1987) Overexpression of the c-erbB-2 oncoprotein in human breast carcinomas: immunohistological assessment correlates with gene amplification. Lancet II:69–72 [DOI] [PubMed] [Google Scholar]
  37. Vijver MJ van de, 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 [DOI] [PubMed] [Google Scholar]
  38. Vogelstein BA (1990) A deadly inheritance. Nature 348:681–682 [DOI] [PubMed] [Google Scholar]
  39. Zeillinger R, Kury F, Czerwenka K, Kubista E, Sliutz G, Knogler W, Huber J, Zielinski C, Reiner G, Jakesz R, et al (1989) HER-2 amplification, steroid receptors and epidermal growth factor receptor in primary breast cancer. Oncogene 4:109–114 [PubMed] [Google Scholar]

Articles from Journal of Cancer Research and Clinical Oncology are provided here courtesy of Springer

RESOURCES