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PARP-1 expression in breast cancer including BRCA1-associated, triple negative and basal-like tumors: possible implications for PARP-1 inhibitor therapy

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Abstract

Despite ongoing trials of PARP inhibitors in the treatment of breast cancer (BC), the extent of poly(ADP-ribose)polymerase-1 (PARP-1) protein expression in BCs, which may influence treatment results, is not known. The purpose of this report is to assess expression of PARP-1 in BC including BRCA1-associated, triple negative (TN), and basal-like tumors. Immunohistochemistry with a PARP-1 antibody on tissue microarrays from 130 BRCA1-associated and 594 BRCA1-non-related BCs was used. The vast majority of breast carcinomas expressed high level of nuclear PARP-1 protein and a small percentage of tumors exhibited both nuclear and cytoplasmic PARP-1 expression. There was a significant difference between the mean nuclear PARP-1 quickscore in BRCA1-associated versus BRCA1-non-associated carcinomas in all tumors (P < 0.0001), in the basal-like group (P = 0.0086), TN (P = 0.0015), and non-basal-like groups (P = 0.016) but not in the non-TN group. Among BRCA1-associated BCs, low PARP-1 expression was found in 18.5% of all cases, 18.9% of basal-like and 21% of TN cancers. Among BRCA1-non-related tumors, low PARP-1 expression was found in 8.8% of all cases, 3.1% of basal-like, and 2.7% of TN cancers. PARP-1 expression is significantly associated with BRCA1 status in basal-like and TN BCs. The assessment of PARP-1 expression in tumor samples may improve the selection of BC patients for PARP inhibitor therapy.

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References

  1. Schreiber V, Dantzer F, Ame JC, de Murcia G (2006) Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol 7:517–528

    Article  PubMed  CAS  Google Scholar 

  2. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, Martin NM, Jackson SP, Smith GC, Ashworth A (2005) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434:917–921

    Article  PubMed  CAS  Google Scholar 

  3. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T (2005) Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434:913–917

    Article  PubMed  CAS  Google Scholar 

  4. Evers B, Drost R, Schut E, de Bruin M, van der Burg E, Derksen PW, Holstege H, Liu X, van Drunen E, Beverloo HB, Smith GC, Martin NM, Lau A, O’Connor MJ, Jonkers J (2008) Selective inhibition of BRCA2-deficient mammary tumor cell growth by AZD2281 and cisplatin. Clin Cancer Res 14:3916–3925

    Article  PubMed  CAS  Google Scholar 

  5. Rottenberg S, Jonkers J (2008) Modeling therapy resistance in genetically engineered mouse cancer models. Drug Resist Updat 11:51–60

    Article  PubMed  CAS  Google Scholar 

  6. Hay T, Matthews JR, Pietzka L, Lau A, Cranston A, Nygren AO, Douglas-Jones A, Smith GC, Martin NM, O’Connor M, Clarke AR (2009) Poly(ADP-ribose) polymerase-1 inhibitor treatment regresses autochthonous Brca2/p53-mutant mammary tumors in vivo and delays tumor relapse in combination with carboplatin. Cancer Res 69:3850–3855

    Article  PubMed  CAS  Google Scholar 

  7. Comen EA, Robson M (2010) Inhibition of poly(ADP)-ribose polymerase as a therapeutic strategy for breast cancer. Oncology (Williston Park) 24:55–62

    Google Scholar 

  8. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O’Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS (2009) Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 361:123–134

    Article  PubMed  CAS  Google Scholar 

  9. Nosho K, Yamamoto H, Mikami M, Taniguchi H, Takahashi T, Adachi Y, Imamura A, Imai K, Shinomura Y (2006) Overexpression of poly(ADP-ribose) polymerase-1 (PARP-1) in the early stage of colorectal carcinogenesis. Eur J Cancer 42:2374–2381

    Article  PubMed  CAS  Google Scholar 

  10. Csete B, Lengyel Z, Kadar Z, Battyani Z (2009) Poly(adenosine diphosphate-ribose) polymerase-1 expression in cutaneous malignant melanomas as a new molecular marker of aggressive tumor. Pathol Oncol Res 15:47–53

    Article  PubMed  CAS  Google Scholar 

  11. Gorski B, Cybulski C, Huzarski T, Byrski T, Gronwald J, Jakubowska A, Stawicka M, Gozdecka-Grodecka S, Szwiec M, Urbanski K, Mitus J, Marczyk E, Dziuba J, Wandzel P, Surdyka D, Haus O, Janiszewska H, Debniak T, Toloczko-Grabarek A, Medrek K, Masojc B, Mierzejewski M, Kowalska E, Narod SA, Lubinski J (2005) Breast cancer predisposing alleles in Poland. Breast Cancer Res Treat 92:19–24

    Article  PubMed  CAS  Google Scholar 

  12. Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19:403–410

    Article  PubMed  CAS  Google Scholar 

  13. Haybittle JL, Blamey RW, Elston CW, Johnson J, Doyle PJ, Campbell FC, Nicholson RI, Griffiths K (1982) A prognostic index in primary breast cancer. Br J Cancer 45:361–366

    Article  PubMed  CAS  Google Scholar 

  14. Detre S, Saclani Jotti G, Dowsett M (1995) A “quickscore” method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol 48:876–878

    Article  PubMed  CAS  Google Scholar 

  15. Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med 131:18–43

    PubMed  CAS  Google Scholar 

  16. Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Arch Pathol Lab Med 134:E1–E16

    Google Scholar 

  17. Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, Akslen LA, Ragaz J, Gown AM, Gilks CB, van de Rijn M, Perou CM (2004) Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10:5367–5374

    Article  PubMed  CAS  Google Scholar 

  18. Cheang MC, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, Perou CM, Nielsen TO (2008) Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res 14:1368–1376

    Article  PubMed  CAS  Google Scholar 

  19. Fu Z, Fenselau C (2005) Proteomic evidence for roles for nucleolin and poly[ADP-ribosyl] transferase in drug resistance. J Proteome Res 4:1583–1591

    Article  PubMed  CAS  Google Scholar 

  20. McCabe N, Cerone MA, Ohishi T, Seimiya H, Lord CJ, Ashworth A (2009) Targeting Tankyrase 1 as a therapeutic strategy for BRCA-associated cancer. Oncogene 28:1465–1470

    Article  PubMed  CAS  Google Scholar 

  21. Bieche I, de Murcia G, Lidereau R (1996) Poly(ADP-ribose) polymerase gene expression status and genomic instability in human breast cancer. Clin Cancer Res 2:1163–1167

    PubMed  CAS  Google Scholar 

  22. Turner NC, Reis-Filho JS, Russell AM, Springall RJ, Ryder K, Steele D, Savage K, Gillett CE, Schmitt FC, Ashworth A, Tutt AN (2007) BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene 26:2126–2132

    Article  PubMed  CAS  Google Scholar 

  23. Inbar-Rozensal D, Castiel A, Visochek L, Castel D, Dantzer F, Izraeli S, Cohen-Armon M (2009) A selective eradication of human nonhereditary breast cancer cells by phenanthridine-derived polyADP-ribose polymerase inhibitors. Breast Cancer Res 11:R78

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This article supported by Pomeranian Medical University Research Program grant #WL-125-01/S/10.

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Correspondence to Wenancjusz Domagala.

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Domagala, P., Huzarski, T., Lubinski, J. et al. PARP-1 expression in breast cancer including BRCA1-associated, triple negative and basal-like tumors: possible implications for PARP-1 inhibitor therapy. Breast Cancer Res Treat 127, 861–869 (2011). https://doi.org/10.1007/s10549-011-1441-2

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  • DOI: https://doi.org/10.1007/s10549-011-1441-2

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