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Erschienen in: Breast Cancer Research and Treatment 3/2010

01.08.2010 | Preclinical study

Clinical relevance of the putative stem cell marker p63 in breast cancer

verfasst von: L. Hanker, T. Karn, E. Ruckhaeberle, R. Gaetje, C. Solbach, M. Schmidt, K. Engels, U. Holtrich, M. Kaufmann, A. Rody

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2010

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Abstract

P63 is a member of the p53 family. This protein is crucial for the maintenance of a stem cell population in the human epithelium and necessary for the normal development of all epithelial tissues including mammary glands. In normal breast tissue, the p63 seems to be a specific myoepithelial cell marker. P63 expression has been described in highly aggressive ER negative basal-like breast tumors. The value of p63 expression in ER positive disease is less clear. The expression levels of p63 mRNA by Affymetrix microarray analysis in a combined cohort of 2,158 ER positive breast cancers and its prognostic and predictive impact were analyzed. Tumor samples containing large amounts of benign breast tissue, which will interfere with p63 measurement, were excluded prior to the analysis. Survival analysis revealed a better prognosis of ER positive breast cancer expressing p63 (n = 410; P < 0.036). No correlation of p63 with standard parameters was observed. In a subgroup analysis, endocrine-treated patients with high p63 expression showed a better prognosis than low p63 expression (P = 0.06; n = 186). In untreated patients, this effect was less clear (n = 148; P = 0.5). P63 is a positive prognostic factor in endocrine-treated ER positive breast cancer and might influence responsiveness to endocrine treatment. Thus, p63 could be helpful as a predictive factor for endocrine therapy.
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Literatur
1.
Zurück zum Zitat McKeon F, Melino G (2007) Fog of war: the emerging p53 family. Cell cycle 6(3):229–232PubMed McKeon F, Melino G (2007) Fog of war: the emerging p53 family. Cell cycle 6(3):229–232PubMed
2.
Zurück zum Zitat Finlan LE, Hupp TR (2007) p63: the phantom of the tumor suppressor. Cell cycle 6(9):1062–1071PubMed Finlan LE, Hupp TR (2007) p63: the phantom of the tumor suppressor. Cell cycle 6(9):1062–1071PubMed
3.
Zurück zum Zitat King KE, Weinberg WC (2007) p63: defining roles in morphogenesis, homeostasis, and neoplasia of the epidermis. Mol Carcinog 46(8):716–724CrossRefPubMed King KE, Weinberg WC (2007) p63: defining roles in morphogenesis, homeostasis, and neoplasia of the epidermis. Mol Carcinog 46(8):716–724CrossRefPubMed
4.
Zurück zum Zitat Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dotsch V, Andrews NC, Caput D, McKeon F (1998) p63, a p53 homolog at 3q27–29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol cell 2(3):305–316CrossRefPubMed Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dotsch V, Andrews NC, Caput D, McKeon F (1998) p63, a p53 homolog at 3q27–29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol cell 2(3):305–316CrossRefPubMed
6.
Zurück zum Zitat Flores ER, Tsai KY, Crowley D, Sengupta S, Yang A, McKeon F, Jacks T (2002) p63 and p73 are required for p53-dependent apoptosis in response to DNA damage. Nature 416(6880):560–564CrossRefPubMed Flores ER, Tsai KY, Crowley D, Sengupta S, Yang A, McKeon F, Jacks T (2002) p63 and p73 are required for p53-dependent apoptosis in response to DNA damage. Nature 416(6880):560–564CrossRefPubMed
7.
Zurück zum Zitat Irwin MS, Kaelin WG Jr (2001) Role of the newer p53 family proteins in malignancy. Apoptosis 6(1–2):17–29CrossRefPubMed Irwin MS, Kaelin WG Jr (2001) Role of the newer p53 family proteins in malignancy. Apoptosis 6(1–2):17–29CrossRefPubMed
8.
Zurück zum Zitat Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT, Tabin C, Sharpe A, Caput D, Crum C et al (1999) p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398(6729):714–718CrossRefPubMed Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT, Tabin C, Sharpe A, Caput D, Crum C et al (1999) p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398(6729):714–718CrossRefPubMed
9.
Zurück zum Zitat McKeon F (2004) p63 and the epithelial stem cell: more than status quo? Genes Dev 18(5):465–469CrossRefPubMed McKeon F (2004) p63 and the epithelial stem cell: more than status quo? Genes Dev 18(5):465–469CrossRefPubMed
10.
Zurück zum Zitat Barbareschi M, Pecciarini L, Cangi MG, Macri E, Rizzo A, Viale G, Doglioni C (2001) p63, a p53 homologue, is a selective nuclear marker of myoepithelial cells of the human breast. Am J Surg Pathol 25(8):1054–1060CrossRefPubMed Barbareschi M, Pecciarini L, Cangi MG, Macri E, Rizzo A, Viale G, Doglioni C (2001) p63, a p53 homologue, is a selective nuclear marker of myoepithelial cells of the human breast. Am J Surg Pathol 25(8):1054–1060CrossRefPubMed
11.
Zurück zum Zitat DiRenzo J, Signoretti S, Nakamura N, Rivera-Gonzalez R, Sellers W, Loda M, Brown M (2002) Growth factor requirements and basal phenotype of an immortalized mammary epithelial cell line. Cancer Res 62(1):89–98PubMed DiRenzo J, Signoretti S, Nakamura N, Rivera-Gonzalez R, Sellers W, Loda M, Brown M (2002) Growth factor requirements and basal phenotype of an immortalized mammary epithelial cell line. Cancer Res 62(1):89–98PubMed
12.
Zurück zum Zitat Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR, Bradley A (1999) p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 398(6729):708–713CrossRefPubMed Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR, Bradley A (1999) p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 398(6729):708–713CrossRefPubMed
13.
Zurück zum Zitat Matos I, Dufloth R, Alvarenga M, Zeferino LC, Schmitt F (2005) p63, cytokeratin 5, and P-cadherin: three molecular markers to distinguish basal phenotype in breast carcinomas. Virchows Arch 447(4):688–694CrossRefPubMed Matos I, Dufloth R, Alvarenga M, Zeferino LC, Schmitt F (2005) p63, cytokeratin 5, and P-cadherin: three molecular markers to distinguish basal phenotype in breast carcinomas. Virchows Arch 447(4):688–694CrossRefPubMed
14.
Zurück zum Zitat Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98(19):10869–10874CrossRefPubMed Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98(19):10869–10874CrossRefPubMed
15.
Zurück zum Zitat Ribeiro-Silva A, Zambelli Ramalho LN, Britto Garcia S, Zucoloto S (2003) The relationship between p63 and p53 expression in normal and neoplastic breast tissue. Arch Pathol Lab Med 127(3):336–340PubMed Ribeiro-Silva A, Zambelli Ramalho LN, Britto Garcia S, Zucoloto S (2003) The relationship between p63 and p53 expression in normal and neoplastic breast tissue. Arch Pathol Lab Med 127(3):336–340PubMed
16.
Zurück zum Zitat Reis-Filho JS, Milanezi F, Paredes J, Silva P, Pereira EM, Maeda SA, De Carvalho LV, Schmitt FC (2003) Novel and classic myoepithelial/stem cell markers in metaplastic carcinomas of the breast. Appl Immunohistochem Mol Morphol 11(1):1–8CrossRefPubMed Reis-Filho JS, Milanezi F, Paredes J, Silva P, Pereira EM, Maeda SA, De Carvalho LV, Schmitt FC (2003) Novel and classic myoepithelial/stem cell markers in metaplastic carcinomas of the breast. Appl Immunohistochem Mol Morphol 11(1):1–8CrossRefPubMed
17.
Zurück zum Zitat Flores ER, Sengupta S, Miller JB, Newman JJ, Bronson R, Crowley D, Yang A, McKeon F, Jacks T (2005) Tumor predisposition in mice mutant for p63 and p73: evidence for broader tumor suppressor functions for the p53 family. Cancer Cell 7(4):363–373CrossRefPubMed Flores ER, Sengupta S, Miller JB, Newman JJ, Bronson R, Crowley D, Yang A, McKeon F, Jacks T (2005) Tumor predisposition in mice mutant for p63 and p73: evidence for broader tumor suppressor functions for the p53 family. Cancer Cell 7(4):363–373CrossRefPubMed
18.
Zurück zum Zitat Keyes WM, Vogel H, Koster MI, Guo X, Qi Y, Petherbridge KM, Roop DR, Bradley A, Mills AA (2006) p63 heterozygous mutant mice are not prone to spontaneous or chemically induced tumors. Proc Natl Acad Sci USA 103(22):8435–8440CrossRefPubMed Keyes WM, Vogel H, Koster MI, Guo X, Qi Y, Petherbridge KM, Roop DR, Bradley A, Mills AA (2006) p63 heterozygous mutant mice are not prone to spontaneous or chemically induced tumors. Proc Natl Acad Sci USA 103(22):8435–8440CrossRefPubMed
19.
Zurück zum Zitat Yamaguchi K, Wu L, Caballero OL, Hibi K, Trink B, Resto V, Cairns P, Okami K, Koch WM, Sidransky D et al (2000) Frequent gain of the p40/p51/p63 gene locus in primary head and neck squamous cell carcinoma. Int J Cancer 86(5):684–689CrossRefPubMed Yamaguchi K, Wu L, Caballero OL, Hibi K, Trink B, Resto V, Cairns P, Okami K, Koch WM, Sidransky D et al (2000) Frequent gain of the p40/p51/p63 gene locus in primary head and neck squamous cell carcinoma. Int J Cancer 86(5):684–689CrossRefPubMed
20.
Zurück zum Zitat Uramoto H, Sugio K, Oyama T, Nakata S, Ono K, Nozoe T, Yasumoto K (2006) Expression of the p53 family in lung cancer. Anticancer Res 26(3A):1785–1790 Uramoto H, Sugio K, Oyama T, Nakata S, Ono K, Nozoe T, Yasumoto K (2006) Expression of the p53 family in lung cancer. Anticancer Res 26(3A):1785–1790
21.
Zurück zum Zitat Takeuchi Y, Tamura A, Kamiya M, Fukuda T, Ishikawa O (2005) Immunohistochemical analyses of p63 expression in cutaneous tumours. Br J Dermatol 153(6):1230–1232CrossRefPubMed Takeuchi Y, Tamura A, Kamiya M, Fukuda T, Ishikawa O (2005) Immunohistochemical analyses of p63 expression in cutaneous tumours. Br J Dermatol 153(6):1230–1232CrossRefPubMed
22.
Zurück zum Zitat Lin Z, Liu M, Li Z, Kim C, Lee E, Kim I (2006) DeltaNp63 protein expression in uterine cervical and endometrial cancers. J Cancer Res Clin Oncol 132(12):811–816CrossRefPubMed Lin Z, Liu M, Li Z, Kim C, Lee E, Kim I (2006) DeltaNp63 protein expression in uterine cervical and endometrial cancers. J Cancer Res Clin Oncol 132(12):811–816CrossRefPubMed
23.
Zurück zum Zitat Quade BJ, Yang A, Wang Y, Sun D, Park J, Sheets EE, Cviko A, Federschneider JM, Peters R, McKeon FD et al (2001) Expression of the p53 homologue p63 in early cervical neoplasia. Gynecol Oncol 80(1):24–29CrossRefPubMed Quade BJ, Yang A, Wang Y, Sun D, Park J, Sheets EE, Cviko A, Federschneider JM, Peters R, McKeon FD et al (2001) Expression of the p53 homologue p63 in early cervical neoplasia. Gynecol Oncol 80(1):24–29CrossRefPubMed
24.
Zurück zum Zitat Reis-Filho JS, Schmitt FC (2003) p63 expression in sarcomatoid/metaplastic carcinomas of the breast. Histopathology 42(1):94–95CrossRefPubMed Reis-Filho JS, Schmitt FC (2003) p63 expression in sarcomatoid/metaplastic carcinomas of the breast. Histopathology 42(1):94–95CrossRefPubMed
25.
Zurück zum Zitat Wang X, Mori I, Tang W, Nakamura M, Nakamura Y, Sato M, Sakurai T, Kakudo K (2002) p63 expression in normal, hyperplastic and malignant breast tissues. Breast Cancer 9(3):216–219 Wang X, Mori I, Tang W, Nakamura M, Nakamura Y, Sato M, Sakurai T, Kakudo K (2002) p63 expression in normal, hyperplastic and malignant breast tissues. Breast Cancer 9(3):216–219
26.
27.
Zurück zum Zitat Karn T, Metzler D, Ruckhaberle E, Hanker L, Gatje R, Solbach C, Ahr A, Schmidt M, Holtrich U, Kaufmann M et al (2009) Data driven derivation of cutoffs from a pool of 3,030 Affymetrix arrays to stratify distinct clinical types of breast cancer. Breast Cancer Res Treat. doi:10.1007/s10549-009-0416-z Karn T, Metzler D, Ruckhaberle E, Hanker L, Gatje R, Solbach C, Ahr A, Schmidt M, Holtrich U, Kaufmann M et al (2009) Data driven derivation of cutoffs from a pool of 3,030 Affymetrix arrays to stratify distinct clinical types of breast cancer. Breast Cancer Res Treat. doi:10.​1007/​s10549-009-0416-z
28.
Zurück zum Zitat Ahr A, Karn T, Solbach C, Seiter T, Strebhardt K, Holtrich U, Kaufmann M (2002) Identification of high risk breast-cancer patients by gene expression profiling. Lancet 359(9301):131–132CrossRefPubMed Ahr A, Karn T, Solbach C, Seiter T, Strebhardt K, Holtrich U, Kaufmann M (2002) Identification of high risk breast-cancer patients by gene expression profiling. Lancet 359(9301):131–132CrossRefPubMed
29.
Zurück zum Zitat Rody A, Holtrich U, Gaetje R, Gehrmann M, Engels K, von Minckwitz G, Loibl S, Diallo-Danebrock R, Ruckhaberle E, Metzler D et al (2007) Poor outcome in estrogen receptor-positive breast cancers predicted by loss of plexin B1 (2007) Clin Cancer Res 13(4):1115–1122 Rody A, Holtrich U, Gaetje R, Gehrmann M, Engels K, von Minckwitz G, Loibl S, Diallo-Danebrock R, Ruckhaberle E, Metzler D et al (2007) Poor outcome in estrogen receptor-positive breast cancers predicted by loss of plexin B1 (2007) Clin Cancer Res 13(4):1115–1122
30.
Zurück zum Zitat Rody A, Karn T, Ruckhaberle E, Hanker L, Metzler D, Muller V, Solbach C, Ahr A, Gatje R, Holtrich U et al (2009) Loss of Plexin B1 is highly prognostic in low proliferating ER positive breast cancers—results of a large scale microarray analysis. Eur J Cancer 45(3):405–413 Rody A, Karn T, Ruckhaberle E, Hanker L, Metzler D, Muller V, Solbach C, Ahr A, Gatje R, Holtrich U et al (2009) Loss of Plexin B1 is highly prognostic in low proliferating ER positive breast cancers—results of a large scale microarray analysis. Eur J Cancer 45(3):405–413
31.
Zurück zum Zitat Rody A, Karn T, Solbach C, Gaetje R, Munnes M, Kissler S, Ruckhaberle E, Minckwitz GV, Loibl S, Holtrich U et al (2007) The erbB2+ cluster of the intrinsic gene set predicts tumor response of breast cancer patients receiving neoadjuvant chemotherapy with docetaxel, doxorubicin and cyclophosphamide within the GEPARTRIO trial. Breast 16(3):235–240CrossRefPubMed Rody A, Karn T, Solbach C, Gaetje R, Munnes M, Kissler S, Ruckhaberle E, Minckwitz GV, Loibl S, Holtrich U et al (2007) The erbB2+ cluster of the intrinsic gene set predicts tumor response of breast cancer patients receiving neoadjuvant chemotherapy with docetaxel, doxorubicin and cyclophosphamide within the GEPARTRIO trial. Breast 16(3):235–240CrossRefPubMed
32.
Zurück zum Zitat Ruckhaberle E, Rody A, Engels K, Gaetje R, von Minckwitz G, Schiffmann S, Grosch S, Geisslinger G, Holtrich U, Karn T et al (2008) Microarray analysis of altered sphingolipid metabolism reveals prognostic significance of sphingosine kinase 1 in breast cancer. Breast Cancer Res Treat 112(1):41–52CrossRefPubMed Ruckhaberle E, Rody A, Engels K, Gaetje R, von Minckwitz G, Schiffmann S, Grosch S, Geisslinger G, Holtrich U, Karn T et al (2008) Microarray analysis of altered sphingolipid metabolism reveals prognostic significance of sphingosine kinase 1 in breast cancer. Breast Cancer Res Treat 112(1):41–52CrossRefPubMed
33.
Zurück zum Zitat Wang Y, Klijn JG, Zhang Y, Sieuwerts AM, Look MP, Yang F, Talantov D, Timmermans M, Meijer-van Gelder ME, Yu J et al (2005) Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 365(9460):671–679PubMed Wang Y, Klijn JG, Zhang Y, Sieuwerts AM, Look MP, Yang F, Talantov D, Timmermans M, Meijer-van Gelder ME, Yu J et al (2005) Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 365(9460):671–679PubMed
34.
Zurück zum Zitat Minn AJ, Gupta GP, Padua D, Bos P, Nguyen DX, Nuyten D, Kreike B, Zhang Y, Wang Y, Ishwaran H et al (2007) Lung metastasis genes couple breast tumor size and metastatic spread. Proc Natl Acad Sci U S A 104(16):6740–6745CrossRefPubMed Minn AJ, Gupta GP, Padua D, Bos P, Nguyen DX, Nuyten D, Kreike B, Zhang Y, Wang Y, Ishwaran H et al (2007) Lung metastasis genes couple breast tumor size and metastatic spread. Proc Natl Acad Sci U S A 104(16):6740–6745CrossRefPubMed
35.
Zurück zum Zitat Creighton CJ, Kent Osborne C, van de Vijver MJ, Foekens JA, Klijn JG, Horlings HM, Nuyten D, Wang Y, Zhang Y, Chamness GC et al (2009) Molecular profiles of progesterone receptor loss in human breast tumors. Breast Cancer Res Treat 114(2):287–299CrossRefPubMed Creighton CJ, Kent Osborne C, van de Vijver MJ, Foekens JA, Klijn JG, Horlings HM, Nuyten D, Wang Y, Zhang Y, Chamness GC et al (2009) Molecular profiles of progesterone receptor loss in human breast tumors. Breast Cancer Res Treat 114(2):287–299CrossRefPubMed
36.
Zurück zum Zitat Schmidt M, Bohm D, von Torne C, Steiner E, Puhl A, Pilch H, Lehr HA, Hengstler JG, Kolbl H, Gehrmann M (2008) The humoral immune system has a key prognostic impact in node-negative breast cancer. Cancer Res 68(13):5405–5413CrossRefPubMed Schmidt M, Bohm D, von Torne C, Steiner E, Puhl A, Pilch H, Lehr HA, Hengstler JG, Kolbl H, Gehrmann M (2008) The humoral immune system has a key prognostic impact in node-negative breast cancer. Cancer Res 68(13):5405–5413CrossRefPubMed
37.
Zurück zum Zitat Desmedt C, Piette F, Loi S, Wang Y, Lallemand F, Haibe-Kains B, Viale G, Delorenzi M, Zhang Y, d’Assignies MS et al (2007) Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. Clin Cancer Res 13(11):3207–3214CrossRefPubMed Desmedt C, Piette F, Loi S, Wang Y, Lallemand F, Haibe-Kains B, Viale G, Delorenzi M, Zhang Y, d’Assignies MS et al (2007) Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. Clin Cancer Res 13(11):3207–3214CrossRefPubMed
38.
Zurück zum Zitat Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J, Nordgren H, Farmer P, Praz V, Haibe-Kains B et al (2006) Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst 98(4):262–272CrossRefPubMed Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J, Nordgren H, Farmer P, Praz V, Haibe-Kains B et al (2006) Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst 98(4):262–272CrossRefPubMed
39.
Zurück zum Zitat Loi S, Haibe-Kains B, Desmedt C, Wirapati P, Lallemand F, Tutt AM, Gillet C, Ellis P, Ryder K, Reid JF et al (2008) Predicting prognosis using molecular profiling in estrogen receptor-positive breast cancer treated with tamoxifen. BMC Genomics 9:239CrossRefPubMed Loi S, Haibe-Kains B, Desmedt C, Wirapati P, Lallemand F, Tutt AM, Gillet C, Ellis P, Ryder K, Reid JF et al (2008) Predicting prognosis using molecular profiling in estrogen receptor-positive breast cancer treated with tamoxifen. BMC Genomics 9:239CrossRefPubMed
40.
Zurück zum Zitat Loi S, Haibe-Kains B, Desmedt C, Lallemand F, Tutt AM, Gillet C, Ellis P, Harris A, Bergh J, Foekens JA et al (2007) Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade. J Clin Oncol 25(10):1239–1246CrossRefPubMed Loi S, Haibe-Kains B, Desmedt C, Lallemand F, Tutt AM, Gillet C, Ellis P, Harris A, Bergh J, Foekens JA et al (2007) Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade. J Clin Oncol 25(10):1239–1246CrossRefPubMed
41.
Zurück zum Zitat Zhang Y, Sieuwerts AM, McGreevy M, Casey G, Cufer T, Paradiso A, Harbeck N, Span PN, Hicks DG, Crowe J et al (2009) The 76-gene signature defines high-risk patients that benefit from adjuvant tamoxifen therapy. Breast Cancer Res Treat 116:303–309 Zhang Y, Sieuwerts AM, McGreevy M, Casey G, Cufer T, Paradiso A, Harbeck N, Span PN, Hicks DG, Crowe J et al (2009) The 76-gene signature defines high-risk patients that benefit from adjuvant tamoxifen therapy. Breast Cancer Res Treat 116:303–309
42.
Zurück zum Zitat Pawitan Y, Bjohle J, Amler L, Borg AL, Egyhazi S, Hall P, Han X, Holmberg L, Huang F, Klaar S et al (2005) Gene expression profiling spares early breast cancer patients from adjuvant therapy: derived and validated in two population-based cohorts. Breast Cancer Res 7(6):R953–R964CrossRefPubMed Pawitan Y, Bjohle J, Amler L, Borg AL, Egyhazi S, Hall P, Han X, Holmberg L, Huang F, Klaar S et al (2005) Gene expression profiling spares early breast cancer patients from adjuvant therapy: derived and validated in two population-based cohorts. Breast Cancer Res 7(6):R953–R964CrossRefPubMed
43.
Zurück zum Zitat Miller LD, Smeds J, George J, Vega VB, Vergara L, Ploner A, Pawitan Y, Hall P, Klaar S, Liu ET et al (2005) An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival. Proc Natl Acad Sci USA 102(38):13550–13555CrossRefPubMed Miller LD, Smeds J, George J, Vega VB, Vergara L, Ploner A, Pawitan Y, Hall P, Klaar S, Liu ET et al (2005) An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival. Proc Natl Acad Sci USA 102(38):13550–13555CrossRefPubMed
44.
Zurück zum Zitat Ivshina AV, George J, Senko O, Mow B, Putti TC, Smeds J, Lindahl T, Pawitan Y, Hall P, Nordgren H et al (2006) Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer. Cancer Res 66(21):10292–10301CrossRefPubMed Ivshina AV, George J, Senko O, Mow B, Putti TC, Smeds J, Lindahl T, Pawitan Y, Hall P, Nordgren H et al (2006) Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer. Cancer Res 66(21):10292–10301CrossRefPubMed
45.
Zurück zum Zitat Chin K, DeVries S, Fridlyand J, Spellman PT, Roydasgupta R, Kuo WL, Lapuk A, Neve RM, Qian Z, Ryder T et al (2006) Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell 10(6):529–541CrossRefPubMed Chin K, DeVries S, Fridlyand J, Spellman PT, Roydasgupta R, Kuo WL, Lapuk A, Neve RM, Qian Z, Ryder T et al (2006) Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell 10(6):529–541CrossRefPubMed
46.
Zurück zum Zitat Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, Viale A, Olshen AB, Gerald WL, Massague J (2005) Genes that mediate breast cancer metastasis to lung. Nature 436(7050):518–524CrossRefPubMed Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, Viale A, Olshen AB, Gerald WL, Massague J (2005) Genes that mediate breast cancer metastasis to lung. Nature 436(7050):518–524CrossRefPubMed
47.
Zurück zum Zitat Hess KR, Anderson K, Symmans WF, Valero V, Ibrahim N, Mejia JA, Booser D, Theriault RL, Buzdar AU, Dempsey PJ et al (2006) Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer. J Clin Oncol 24(26):4236–4244CrossRefPubMed Hess KR, Anderson K, Symmans WF, Valero V, Ibrahim N, Mejia JA, Booser D, Theriault RL, Buzdar AU, Dempsey PJ et al (2006) Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer. J Clin Oncol 24(26):4236–4244CrossRefPubMed
48.
Zurück zum Zitat Farmer P, Bonnefoi H, Becette V, Tubiana-Hulin M, Fumoleau P, Larsimont D, Macgrogan G, Bergh J, Cameron D, Goldstein D et al (2005) Identification of molecular apocrine breast tumours by microarray analysis. Oncogene 24(29):4660–4671CrossRefPubMed Farmer P, Bonnefoi H, Becette V, Tubiana-Hulin M, Fumoleau P, Larsimont D, Macgrogan G, Bergh J, Cameron D, Goldstein D et al (2005) Identification of molecular apocrine breast tumours by microarray analysis. Oncogene 24(29):4660–4671CrossRefPubMed
49.
Zurück zum Zitat Miller WR, Larionov AA, Renshaw L, Anderson TJ, White S, Murray J, Murray E, Hampton G, Walker JR, Ho S et al (2007) Changes in breast cancer transcriptional profiles after treatment with the aromatase inhibitor, letrozole. Pharmacogenet Genomics 17(10):813–826CrossRefPubMed Miller WR, Larionov AA, Renshaw L, Anderson TJ, White S, Murray J, Murray E, Hampton G, Walker JR, Ho S et al (2007) Changes in breast cancer transcriptional profiles after treatment with the aromatase inhibitor, letrozole. Pharmacogenet Genomics 17(10):813–826CrossRefPubMed
51.
Zurück zum Zitat Yu K, Ganesan K, Tan LK, Laban M, Wu J, Zhao XD, Li H, Leung CH, Zhu Y, Wei CL et al (2008) A precisely regulated gene expression cassette potently modulates metastasis and survival in multiple solid cancers. PLoS Genet 4(7):e1000129CrossRefPubMed Yu K, Ganesan K, Tan LK, Laban M, Wu J, Zhao XD, Li H, Leung CH, Zhu Y, Wei CL et al (2008) A precisely regulated gene expression cassette potently modulates metastasis and survival in multiple solid cancers. PLoS Genet 4(7):e1000129CrossRefPubMed
53.
Zurück zum Zitat Richardson AL, Wang ZC, De Nicolo A, Lu X, Brown M, Miron A, Liao X, Iglehart JD, Livingston DM, Ganesan S (2006) X chromosomal abnormalities in basal-like human breast cancer. Cancer Cell 9(2):121–132CrossRefPubMed Richardson AL, Wang ZC, De Nicolo A, Lu X, Brown M, Miron A, Liao X, Iglehart JD, Livingston DM, Ganesan S (2006) X chromosomal abnormalities in basal-like human breast cancer. Cancer Cell 9(2):121–132CrossRefPubMed
54.
Zurück zum Zitat Klein A, Wessel R, Graessmann M, Jurgens M, Petersen I, Schmutzler R, Niederacher D, Arnold N, Meindl A, Scherneck S et al (2007) Comparison of gene expression data from human and mouse breast cancers: identification of a conserved breast tumor gene set. Int J Cancer 121(3):683–688CrossRefPubMed Klein A, Wessel R, Graessmann M, Jurgens M, Petersen I, Schmutzler R, Niederacher D, Arnold N, Meindl A, Scherneck S et al (2007) Comparison of gene expression data from human and mouse breast cancers: identification of a conserved breast tumor gene set. Int J Cancer 121(3):683–688CrossRefPubMed
55.
Zurück zum Zitat Marty B, Maire V, Gravier E, Rigaill G, Vincent-Salomon A, Kappler M, Lebigot I, Djelti F, Tourdes A, Gestraud P et al (2008) Frequent PTEN genomic alterations and activated phosphatidylinositol 3-kinase pathway in basal-like breast cancer cells. Breast Cancer Res 10(6):R101CrossRefPubMed Marty B, Maire V, Gravier E, Rigaill G, Vincent-Salomon A, Kappler M, Lebigot I, Djelti F, Tourdes A, Gestraud P et al (2008) Frequent PTEN genomic alterations and activated phosphatidylinositol 3-kinase pathway in basal-like breast cancer cells. Breast Cancer Res 10(6):R101CrossRefPubMed
56.
Zurück zum Zitat Chen DT, Nasir A, Culhane A, Venkataramu C, Fulp W, Rubio R, Wang T, Agrawal D, McCarthy SM, Gruidl M et al (2009) Proliferative genes dominate malignancy-risk gene signature in histologically-normal breast tissue. Breast Cancer Res Treat. doi:10.1007/s10549-009-0344-y Chen DT, Nasir A, Culhane A, Venkataramu C, Fulp W, Rubio R, Wang T, Agrawal D, McCarthy SM, Gruidl M et al (2009) Proliferative genes dominate malignancy-risk gene signature in histologically-normal breast tissue. Breast Cancer Res Treat. doi:10.​1007/​s10549-009-0344-y
57.
Zurück zum Zitat Affymetrix (2001) Statistical algorithms reference guide, Technical report. Affymetrix, Santa Clara Affymetrix (2001) Statistical algorithms reference guide, Technical report. Affymetrix, Santa Clara
58.
Zurück zum Zitat Gautier L, Cope L, Bolstad BM, Irizarry RA (2004) affy—analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20(3):307–315CrossRefPubMed Gautier L, Cope L, Bolstad BM, Irizarry RA (2004) affy—analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20(3):307–315CrossRefPubMed
59.
Zurück zum Zitat Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J et al (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5(10):R80 Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J et al (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5(10):R80
60.
Zurück zum Zitat Barbieri CE, Tang LJ, Brown KA, Pietenpol JA (2006) Loss of p63 leads to increased cell migration and up-regulation of genes involved in invasion and metastasis. Cancer Res 66(15):7589–7597 Barbieri CE, Tang LJ, Brown KA, Pietenpol JA (2006) Loss of p63 leads to increased cell migration and up-regulation of genes involved in invasion and metastasis. Cancer Res 66(15):7589–7597
61.
Zurück zum Zitat Yang A, Zhu Z, Kapranov P, McKeon F, Church GM, Gingeras TR, Struhl K (2006) Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells. Mol Cell 24(4):593–602 Yang A, Zhu Z, Kapranov P, McKeon F, Church GM, Gingeras TR, Struhl K (2006) Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells. Mol Cell 24(4):593–602
62.
Zurück zum Zitat McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2006) REporting recommendations for tumor MARKer prognostic studies (REMARK). Breast Cancer Res Treat 100(2):229–235CrossRefPubMed McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2006) REporting recommendations for tumor MARKer prognostic studies (REMARK). Breast Cancer Res Treat 100(2):229–235CrossRefPubMed
63.
Zurück zum Zitat Debus E, Weber K, Osborn M (1982) Monoclonal cytokeratin antibodies that distinguish simple from stratified squamous epithelia: characterization on human tissues. The EMBO journal 1(12):1641–1647PubMed Debus E, Weber K, Osborn M (1982) Monoclonal cytokeratin antibodies that distinguish simple from stratified squamous epithelia: characterization on human tissues. The EMBO journal 1(12):1641–1647PubMed
64.
Zurück zum Zitat Nagle RB, Bocker W, Davis JR, Heid HW, Kaufmann M, Lucas DO, Jarasch ED (1986) Characterization of breast carcinomas by two monoclonal antibodies distinguishing myoepithelial from luminal epithelial cells. J Histochem Cytochem 34(7):869–881PubMed Nagle RB, Bocker W, Davis JR, Heid HW, Kaufmann M, Lucas DO, Jarasch ED (1986) Characterization of breast carcinomas by two monoclonal antibodies distinguishing myoepithelial from luminal epithelial cells. J Histochem Cytochem 34(7):869–881PubMed
65.
Zurück zum Zitat Abd El-Rehim DM, Pinder SE, Paish CE, Bell J, Blamey RW, Robertson JF, Nicholson RI, Ellis IO (2004) Expression of luminal and basal cytokeratins in human breast carcinoma. J Pathol 203(2):661–671CrossRefPubMed Abd El-Rehim DM, Pinder SE, Paish CE, Bell J, Blamey RW, Robertson JF, Nicholson RI, Ellis IO (2004) Expression of luminal and basal cytokeratins in human breast carcinoma. J Pathol 203(2):661–671CrossRefPubMed
66.
Zurück zum Zitat Ribeiro-Silva A, Ramalho LN, Garcia SB, Brandao DF, Chahud F, Zucoloto S (2005) p63 correlates with both BRCA1 and cytokeratin 5 in invasive breast carcinomas: further evidence for the pathogenesis of the basal phenotype of breast cancer. Histopathology 47(5):458–466CrossRefPubMed Ribeiro-Silva A, Ramalho LN, Garcia SB, Brandao DF, Chahud F, Zucoloto S (2005) p63 correlates with both BRCA1 and cytokeratin 5 in invasive breast carcinomas: further evidence for the pathogenesis of the basal phenotype of breast cancer. Histopathology 47(5):458–466CrossRefPubMed
67.
Zurück zum Zitat Reis-Filho JS, Simpson PT, Martins A, Preto A, Gartner F, Schmitt FC (2003) Distribution of p63, cytokeratins 5/6 and cytokeratin 14 in 51 normal and 400 neoplastic human tissue samples using TARP-4 multi-tumor tissue microarray. Virchows Arch 443(2):122–132CrossRefPubMed Reis-Filho JS, Simpson PT, Martins A, Preto A, Gartner F, Schmitt FC (2003) Distribution of p63, cytokeratins 5/6 and cytokeratin 14 in 51 normal and 400 neoplastic human tissue samples using TARP-4 multi-tumor tissue microarray. Virchows Arch 443(2):122–132CrossRefPubMed
68.
Zurück zum Zitat Czkowski KA, Ferguson KL, Grier DD, Hossain D, Banerjee SS, McNeal JE, Bostwick DG (2003) Adenoid cystic/basal cell carcinoma of the prostate: clinicopathologic findings in 19 cases. Am J Surg Pathol 27(12):1523–1529CrossRef Czkowski KA, Ferguson KL, Grier DD, Hossain D, Banerjee SS, McNeal JE, Bostwick DG (2003) Adenoid cystic/basal cell carcinoma of the prostate: clinicopathologic findings in 19 cases. Am J Surg Pathol 27(12):1523–1529CrossRef
69.
Zurück zum Zitat Hibi K, Trink B, Patturajan M, Westra WH, Caballero OL, Hill DE, Ratovitski EA, Jen J, Sidransky D (2000) AIS is an oncogene amplified in squamous cell carcinoma. Proc Natl Acad Sci USA 97(10):5462–5467CrossRefPubMed Hibi K, Trink B, Patturajan M, Westra WH, Caballero OL, Hill DE, Ratovitski EA, Jen J, Sidransky D (2000) AIS is an oncogene amplified in squamous cell carcinoma. Proc Natl Acad Sci USA 97(10):5462–5467CrossRefPubMed
70.
Zurück zum Zitat Senoo M, Tsuchiya I, Matsumura Y, Mori T, Saito Y, Kato H, Okamoto T, Habu S (2001) Transcriptional dysregulation of the p73L/p63/p51/p40/KET gene in human squamous cell carcinomas: expression of Delta Np73L, a novel dominant-negative isoform, and loss of expression of the potential tumour suppressor p51. Br J Cancer 84(9):1235–1241CrossRefPubMed Senoo M, Tsuchiya I, Matsumura Y, Mori T, Saito Y, Kato H, Okamoto T, Habu S (2001) Transcriptional dysregulation of the p73L/p63/p51/p40/KET gene in human squamous cell carcinomas: expression of Delta Np73L, a novel dominant-negative isoform, and loss of expression of the potential tumour suppressor p51. Br J Cancer 84(9):1235–1241CrossRefPubMed
71.
Zurück zum Zitat Pruneri G, Pignataro L, Manzotti M, Carboni N, Ronchetti D, Neri A, Cesana BM, Viale G (2002) p63 in laryngeal squamous cell carcinoma: evidence for a role of TA-p63 down-regulation in tumorigenesis and lack of prognostic implications of p63 immunoreactivity. Lab Investig 82(10):1327–1334PubMed Pruneri G, Pignataro L, Manzotti M, Carboni N, Ronchetti D, Neri A, Cesana BM, Viale G (2002) p63 in laryngeal squamous cell carcinoma: evidence for a role of TA-p63 down-regulation in tumorigenesis and lack of prognostic implications of p63 immunoreactivity. Lab Investig 82(10):1327–1334PubMed
72.
Zurück zum Zitat Chen YK, Hsue SS, Lin LM (2004) Expression of p63 (TA and deltaN isoforms) in human primary well differentiated buccal carcinomas. Int J Oral Maxillofac Surg 33(5):493–497CrossRefPubMed Chen YK, Hsue SS, Lin LM (2004) Expression of p63 (TA and deltaN isoforms) in human primary well differentiated buccal carcinomas. Int J Oral Maxillofac Surg 33(5):493–497CrossRefPubMed
73.
Zurück zum Zitat Zangen R, Ratovitski E, Sidransky D (2005) DeltaNp63alpha levels correlate with clinical tumor response to cisplatin. Cell cycle 4(10):1313–1315PubMed Zangen R, Ratovitski E, Sidransky D (2005) DeltaNp63alpha levels correlate with clinical tumor response to cisplatin. Cell cycle 4(10):1313–1315PubMed
74.
Zurück zum Zitat Rocco JW, Leong CO, Kuperwasser N, DeYoung MP, Ellisen LW (2006) p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis. Cancer Cell 9(1):45–56CrossRefPubMed Rocco JW, Leong CO, Kuperwasser N, DeYoung MP, Ellisen LW (2006) p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis. Cancer Cell 9(1):45–56CrossRefPubMed
75.
Zurück zum Zitat DeYoung MP, Johannessen CM, Leong CO, Faquin W, Rocco JW, Ellisen LW (2006) Tumor-specific p73 up-regulation mediates p63 dpendence in squamous cell carcinoma. Cancer Res 66(19):9362–9368 DeYoung MP, Johannessen CM, Leong CO, Faquin W, Rocco JW, Ellisen LW (2006) Tumor-specific p73 up-regulation mediates p63 dpendence in squamous cell carcinoma. Cancer Res 66(19):9362–9368
76.
Zurück zum Zitat Leong CO, Vidnovic N, DeYoung MP, Sgroi D, Ellisen LW (2007) The p63/p73 network mediates chemosensitivity to cisplatin in a biologically defined subset of primary breast cancers. J Clin Investig 117(5):1370–1380CrossRefPubMed Leong CO, Vidnovic N, DeYoung MP, Sgroi D, Ellisen LW (2007) The p63/p73 network mediates chemosensitivity to cisplatin in a biologically defined subset of primary breast cancers. J Clin Investig 117(5):1370–1380CrossRefPubMed
Metadaten
Titel
Clinical relevance of the putative stem cell marker p63 in breast cancer
verfasst von
L. Hanker
T. Karn
E. Ruckhaeberle
R. Gaetje
C. Solbach
M. Schmidt
K. Engels
U. Holtrich
M. Kaufmann
A. Rody
Publikationsdatum
01.08.2010
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 3/2010
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-009-0608-6

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