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Research Article

Testing of Functional Integrity of p53 Protein in Primary Breast Cancer by a Rapid Quantitative p53-p21WAF1 Double Assay May Improve the Clinical Value of p53

Westhof G.a · Olbrecht M.a · Wolff M.b · Schiermeier S.a · Zimmermann R.C.c · Hatzmann W.a

Author affiliations

aDepartment of Obstetrics and Gynecology and bInstitute of Microbiology and Virology, University of Witten/Herdecke School of Medicine, Witten, Germany; cColumbia University, Division of Reproductive Endocrinology, New York, N.Y., USA

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Tumor Biol 2006;27:252–260

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Article / Publication Details

First-Page Preview
Abstract of Research Article

Received: August 03, 2005
Accepted: March 01, 2006
Published online: August 23, 2006
Issue release date: August 2006

Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 4

ISSN: 1010-4283 (Print)
eISSN: 1423-0380 (Online)

For additional information: https://www.karger.com/TBI

Abstract

We hypothesized that inclusion of p21WAF1, an indicator of biological function, into the p53 assay might improve the clinical value of p53 in breast cancer diagnosis.In primary breast carcinomas (n = 146) and healthy/benign controls (n = 40), the p53 protein was quantified by luminescence immunoassay. The p21 protein was simultaneously measured by quantitative ELISA in a representative subgroup of breast cancers (n = 52) and controls (n = 17). In controls, p53 but not p21 was detectable. In almost all cancer tissues, p53 and p21 expression could be quantified. There was no correlation between the concentrations of both proteins. However, if p53 exceeded a threshold of 1.0 ng/mg protein, p21 expression was significantly reduced compared with samples with p53 below threshold. p21 was normally distributed in the low-p53 subpopulation, but not in the high-p53 group. The histologic parameter ‘grade III’ was more often found (p = 0.002) in tumors with p53 >1.0 ng/mg protein than in those with p53 below the threshold. Histological criteria of high tumor malignancy were found more often in cases with high p53 but low p21. Consequently, in clinical routine, a quantitative double assay of p53 and p21WAF1 might help to discriminate breast cancers with preserved or impaired/lost p53 function.

© 2006 S. Karger AG, Basel


References

  1. Nigro JM, Baker SJ, Presinger AC, Jessup JM, Hostetter R, Clearly K, Bigner SH, Davidson N, Baylin S, Devilee P: Mutations in the p53 gene occur in diverse human tumour types. Nature 1989;342:705–708.
  2. Levine AJ, Perry ME, Chang A, Silver A, Dittmer D, Wu M, Welsh D: The 1993 Walter Hubert Lecture: the role of the p53 tumour-suppressor gene in tumorigenesis. Br J Cancer 1994;69:409–416.
  3. Sjögren S, Inganäs M, Norberg T, Lindgren A, Nordgren H, Holmberg L, Bergh J: The p53 gene in breast cancer: prognostic value of complementary DNA sequencing versus immunohistochemistry. J Natl Cancer Inst 1996;88:173–182.
  4. Orita M, Iwahana H, Kanazawa H, Hayashi K, Sekiya T: Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci USA 1989;86:2766–2770.
  5. Tamura G, Kihana T, Nomura K, Terada M, Sugimura T, Hirohashi S: Detection of frequent p53 gene mutations in primary gastric cancer by cell sorting and polymerase chain reaction single-strand conformation polymorphism analysis. Cancer Res 1991;51:3056–3058.
  6. Scholz RB, Milde-Langosch K, Jung R, Schlechte H, Kabisch H, Wagener C, Löning T: Rapid screening for Tp53 mutations by temperature gradient gel electrophoresis: a comparison with SSCP analysis. Hum Mol Gen 1993;2:2155–2158.
  7. Sommer SS, Cunnigham J, McGovern RM, Saitoh S, Schroeder JJ, Wold LE, Kovach JS: Pattern of p53 gene mutations in breast cancers of women of the midwestern United States. J Natl Cancer Inst 1992;84:246–252.
  8. Rodrigues NR, Rowan A, Smith ME, Kerr IB, Bodmer WF, Gannon JV, Lane DP: p53 mutations in colorectal cancer. Proc Natl Acad Sci USA 1990;87:7555–7559.
  9. Bartek J, Bartkova J, Vojtesek B, Staskova Z, Lucas J, Rejthar A, Kovarik J, Midgley CA, Gannon JV, Lane DP: Aberrant expression of the p53 oncoprotein is a common feature of a wide spectrum of human malignancies. Oncogene 1991;6:1699–1703.
  10. Midgley CA, Lane DP: p53 protein stability in tumour cells is not determined by mutation but is dependent on Mdm2 binding. Oncogene 1998;15:1179–1189.
  11. Dowell SP, Hall PA: The p53 tumour suppressor gene and tumour prognosis: is there a relationship (editorial)? J Pathol 1995;177:221–224.
  12. Hall PA, Lane DP: p53 in tumour pathology: can we trust immunohistochemistry? – Revisited! J Pathol 1994;172:1–4.
  13. Berns EMJJ, van Staveren IL, Look MP, Smid M, Klijn JGM, Foekens JA: Mutations in residues of TP53 that directly contact DNA predict poor outcome in human primary breast cancer. Br J Cancer 1998;77:1130–1136.
  14. El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer E, Kinzler KW, Vogelstein B: WAF1, a potential mediator of p53 tumor suppression. Cell 1993;75:817–825.
  15. Weinberg W, Denning M: p21WAF1 control of epithelial cell cycle and cell fate. Crit Rev Oral Biol Med 2002;13:453–462.
  16. Liu S, Bishop WR, Liu M: Differential effects of cell cycle regulatory protein p21WAF1/CIP1 on apoptosis and sensitivity to cancer chemotherapy (review). Drug Resist Updat 2003;6:183–195.
  17. Borg A, Lennerstrand J, Stenmark-Askmalm, Fernö M, Brisfors A, Öhrvik A, Stal O, Killander D, Lane D, Brundell J: Prognostic significance of p53 overexpression in primary breast cancer; a novel luminometric immunoassay applicable on steroid receptor cytosols. Br J Cancer 1995;71:1013–1017.
  18. Westhof G, Bader W, Greiner-Mai E, Hatzmann W: Comparison of cytosolic p53 protein levels in female genital tract, female breast, and their tumors. Tumor Biol 2000;21:123–134.
  19. Westhof G, Salmassi A, Mettler L, Jonat W: Quantitative p53-Proteinbestimmung in benignen Mammageweben, Mammakarzinomen und axillären Lymphknotenmetastasen. Geburtsh Frauenheilk 1997;57:342–348.
    External Resources
  20. Bloom HJC, Richardson WW: Histologic grading and prognosis in breast cancer. Br J Cancer 1957;11:359–377.
  21. Jänicke F, Diedrich K, Jonat W, Gerber B, Lisboa B, Friedrich M, Reimer T, Maas N: St. Gallen 2005: Konsens und klinische Praxis. Frauenarzt 2005;46:182–189.
  22. De Witte HH, Foekens JA, Lennerstrand J, Smid M, Look MP, Klijn JG, Benraad TJ, Berns EM: Prognostic significance of TP53 accumulation in human primary breast cancer: comparison between a rapid quantitative immunoassay and SSCP analysis. Int J Cancer 1996;69:125–130.
  23. Berns EM, De Witte HH, Klijn JG, Willman K, Look MP, Meijer-Van Gelder ME, Benraad TJ, Foekens FA: Prognostic value of TP53 protein accumulation in human primary breast cancer: an analysis by luminometric immunoassay on 1491 tumor cytosols. Anticancer Res 1997;17:3003–3006.
  24. Schuyer M, Henzen-Logmans SC, van der Burg ME, Fieret EJ, Klijn JG, Foekens JA, Berns EM: High prevalence of codon 213Arg → stop mutations of the TP53 gene in human ovarian cancer in the southwestern part of The Netherlands. Int J Cancer 1998;76:299–303.
  25. Werness BA, Freedman AN, Piver MS, Romero-Gutierrez, Petrow E: Prognostic significance of p53 and p21waf1/cip1 immunoreactivity in epithelial cancers of the ovary. Gynecol Oncol 1999;75:413–418.
  26. Cox LS: Multiple pathways control cell growth and transformation: overlapping and independent activities of p53 and p21Cip1/WAF1/Sdi1. J Pathol 1997;183:134–140.
  27. Shoji T, Tanaka F, Takata T, Yanagihara K, Otake Y, Hanaoka N, Miyahara R, Nakagawa T, Kawano Y, Ishikawa S, Katakura H, Wada H: Clinical significance of p21 expression in non-small-cell lung cancer. J Clin Oncol 2002;20:3865–3871.
  28. Geisler HE, Geisler JP, Miller GA, Geisler MJ, Wiemann MC, Zhou Z, Crabtree W: p21 and p53 in ovarian carcinoma: their combined staining is more valuable than either alone. Cancer 2001;92:781–786.
  29. Domagala W, Welcker M, Chosia M, Karbowniczek M, Harezga B, Bartkova J, Bartek J, Osborn M: p21/WAF1/Cip1 expression in invasive ductal breast carcinoma: relationship to p53, proliferation rate, and survival at 5 years. Virchows Arch 2001;439:132–140.
  30. Rose SL, Goodheart MJ, DeYoung BR, Smith BJ, Buller RE: p21 expression predicts outcome in p53-null ovarian carcinomas. Clin Cancer Res 2003;9:1028–1032.
  31. Zhang Y, Fujita N, Tsuruo T: Caspase-mediated cleavage of p21Waf1/Cip1 converts cancer cells from growth arrest to undergoing apoptosis. Oncogene 1999;18:1131–1138.

Article / Publication Details

First-Page Preview
Abstract of Research Article

Received: August 03, 2005
Accepted: March 01, 2006
Published online: August 23, 2006
Issue release date: August 2006

Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 4

ISSN: 1010-4283 (Print)
eISSN: 1423-0380 (Online)

For additional information: https://www.karger.com/TBI


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