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Erschienen in: Breast Cancer Research and Treatment 2/2008

01.05.2008 | Epidemiology

Prevalence and prognostic and predictive relevance of PRAME in breast cancer

verfasst von: Padraig Doolan, Martin Clynes, Susan Kennedy, Jai Prakash Mehta, John Crown, Lorraine O’Driscoll

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2008

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Abstract

Preferentially expressed antigen of melanoma (PRAME) has been described as a potential candidate for immunotherapeutic targeting. However, the prognostic and predictive relevance of PRAME in breast cancer has never been investigated. PRAME gene expression was evaluated in 103 breast tumour biopsies, using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Normal breast tissue was also analysed for comparative purposes. All qRT-PCRs were performed in triplicate. Kaplan–Meier survival curves, Chi-squared and Cox Regression analyses were used to identify associations between PRAME expression and patients’ clinicopathological and survival data. PRAME mRNA was detected in ∼53% of tumour specimens and 37% of normal breast specimens. Kaplan–Meier analysis showed expression of PRAME to correlate significantly with unfavourable disease outcome for patients, in terms of both their disease-free survival (p = 0.0004) and overall survival (OS) (p = 0.0052) times from diagnosis. Multivariate analysis indicated PRAME expression to be an independent prognostic factor for shortened disease-free survival (p = 0.026) and OS (p = 0.02). Furthermore, for patients who received adjuvant chemotherapy, significantly (p = 0.0291) shorter relapse-free survival was achieved for those whose tumour expressed PRAME, compared to those that did not express this transcript. Our results suggest that PRAME mRNA expression may be a useful prognostic and predictive marker for breast cancer.
Literatur
1.
Zurück zum Zitat Ikeda H, Lethe B, Lehmann F et al (1997) Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. Immunity 6:199–208PubMedCrossRef Ikeda H, Lethe B, Lehmann F et al (1997) Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. Immunity 6:199–208PubMedCrossRef
2.
Zurück zum Zitat Epping MT, Wang L, Edel MJ, Carlee L, Hernandez M, Bernards R (2005) The human tumour antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell 122:835–847PubMedCrossRef Epping MT, Wang L, Edel MJ, Carlee L, Hernandez M, Bernards R (2005) The human tumour antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell 122:835–847PubMedCrossRef
3.
Zurück zum Zitat Epping MT, Bernards R (2006) A causal role for the human tumour antigen preferentially expressed antigen of melanoma in cancer. Cancer Res 66:10639–10642PubMedCrossRef Epping MT, Bernards R (2006) A causal role for the human tumour antigen preferentially expressed antigen of melanoma in cancer. Cancer Res 66:10639–10642PubMedCrossRef
4.
Zurück zum Zitat Neumann E, Engelsberg A, Decker J et al (1998) Heterogeneous expression of the tumour-associated antigens RAGE-1, PRAME, and glycoprotein 75 in human renal cell carcinoma: candidates for T-cell-based immunotherapies? Cancer Res 58:4090–4095PubMed Neumann E, Engelsberg A, Decker J et al (1998) Heterogeneous expression of the tumour-associated antigens RAGE-1, PRAME, and glycoprotein 75 in human renal cell carcinoma: candidates for T-cell-based immunotherapies? Cancer Res 58:4090–4095PubMed
5.
Zurück zum Zitat Li CM, Guo M, Borczuk A et al (2002) Gene expression in Wilms’ tumour mimics the earliest committed stage in the metanephric mesenchymal-epithelial transition. Am J Pathol 160:2181–2190PubMed Li CM, Guo M, Borczuk A et al (2002) Gene expression in Wilms’ tumour mimics the earliest committed stage in the metanephric mesenchymal-epithelial transition. Am J Pathol 160:2181–2190PubMed
6.
Zurück zum Zitat Matsushita M, Yamazaki R, Kawakami Y (2004) Quantitative analysis of PRAME for detection of minimal residual disease in leukaemia. Methods Mol Med 97:267–275PubMed Matsushita M, Yamazaki R, Kawakami Y (2004) Quantitative analysis of PRAME for detection of minimal residual disease in leukaemia. Methods Mol Med 97:267–275PubMed
7.
Zurück zum Zitat Oberthuer A, Hero B, Spitz R, Berthold F, Fischer M (2004) The tumour-associated antigen PRAME is universally expressed in high-stage neuroblastoma and associated with poor outcome. Clin Cancer Res 10:4307–4313PubMedCrossRef Oberthuer A, Hero B, Spitz R, Berthold F, Fischer M (2004) The tumour-associated antigen PRAME is universally expressed in high-stage neuroblastoma and associated with poor outcome. Clin Cancer Res 10:4307–4313PubMedCrossRef
8.
Zurück zum Zitat Proto-Siqueira R, Figueiredo-Pontes LL, Panepucci RA et al (2006) PRAME is a membrane and cytoplasmic protein aberrantly expressed in chronic lymphocytic leukemia and mantle cell lymphoma. Leuk Res 30:1333–1339PubMedCrossRef Proto-Siqueira R, Figueiredo-Pontes LL, Panepucci RA et al (2006) PRAME is a membrane and cytoplasmic protein aberrantly expressed in chronic lymphocytic leukemia and mantle cell lymphoma. Leuk Res 30:1333–1339PubMedCrossRef
9.
Zurück zum Zitat Page DL, Andersen AT (1987) Diagnostic histopathology. Churchill Livingstone, London, Melbourne and New York Page DL, Andersen AT (1987) Diagnostic histopathology. Churchill Livingstone, London, Melbourne and New York
10.
Zurück zum Zitat 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 403–410 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 403–410
11.
Zurück zum Zitat Sobin LH, Wittekind C (1997) TNM Classification of Malignant tumours. Wiley, New York Sobin LH, Wittekind C (1997) TNM Classification of Malignant tumours. Wiley, New York
12.
Zurück zum Zitat Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T). Methods 25:402–408PubMedCrossRef Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T). Methods 25:402–408PubMedCrossRef
13.
Zurück zum Zitat van Baren N, Chambost H, Ferrant A et al (1998) PRAME, a gene encoding an antigen recognized on a human melanoma by cytolytic T cells, is expressed in acute leukaemia cells. Br J Haematol 102:1376–1379PubMedCrossRef van Baren N, Chambost H, Ferrant A et al (1998) PRAME, a gene encoding an antigen recognized on a human melanoma by cytolytic T cells, is expressed in acute leukaemia cells. Br J Haematol 102:1376–1379PubMedCrossRef
14.
Zurück zum Zitat Watari K, Tojo A, Nagamura-Inoue T et al (2000) Identification of a melanoma antigen, PRAME, as a BCR/ABL-inducible gene. FEBS Lett 466:367–371PubMedCrossRef Watari K, Tojo A, Nagamura-Inoue T et al (2000) Identification of a melanoma antigen, PRAME, as a BCR/ABL-inducible gene. FEBS Lett 466:367–371PubMedCrossRef
15.
Zurück zum Zitat McElwaine S, Mulligan C, Groet J et al (2004) Microarray transcript profiling distinguishes the transient from the acute type of megakaryoblastic leukaemia (M7) in Down’s syndrome, revealing PRAME as a specific discriminating marker. Br J Haematol 125:729–742PubMedCrossRef McElwaine S, Mulligan C, Groet J et al (2004) Microarray transcript profiling distinguishes the transient from the acute type of megakaryoblastic leukaemia (M7) in Down’s syndrome, revealing PRAME as a specific discriminating marker. Br J Haematol 125:729–742PubMedCrossRef
16.
Zurück zum Zitat Paydas S, Tanriverdi K, Yavuz S, Disel U, Baslamisli F, Burgut R (2005) PRAME mRNA levels in cases with acute leukemia: clinical importance and future prospects. Am J Hematol 79:257–261PubMedCrossRef Paydas S, Tanriverdi K, Yavuz S, Disel U, Baslamisli F, Burgut R (2005) PRAME mRNA levels in cases with acute leukemia: clinical importance and future prospects. Am J Hematol 79:257–261PubMedCrossRef
17.
Zurück zum Zitat Tajeddine N, Millard I, Gailly P, Gala JL (2006) Real-time RT-PCR quantification of PRAME gene expression for monitoring minimal residual disease in acute myeloblastic leukaemia. Clin Chem Lab Med 44:548–555PubMedCrossRef Tajeddine N, Millard I, Gailly P, Gala JL (2006) Real-time RT-PCR quantification of PRAME gene expression for monitoring minimal residual disease in acute myeloblastic leukaemia. Clin Chem Lab Med 44:548–555PubMedCrossRef
18.
Zurück zum Zitat Steinbach D, Hermann J, Viehmann S, Zintl F, Gruhn B (2002) Clinical implications of PRAME gene expression in childhood acute myeloid leukemia. Cancer Genet Cytogenet 133:118–123PubMedCrossRef Steinbach D, Hermann J, Viehmann S, Zintl F, Gruhn B (2002) Clinical implications of PRAME gene expression in childhood acute myeloid leukemia. Cancer Genet Cytogenet 133:118–123PubMedCrossRef
19.
Zurück zum Zitat Steinbach D, Viehmann S, Zintl F, Gruhn B (2002) PRAME gene expression in childhood acute lymphoblastic leukemia. Cancer Genet Cytogenet 138:89–91PubMedCrossRef Steinbach D, Viehmann S, Zintl F, Gruhn B (2002) PRAME gene expression in childhood acute lymphoblastic leukemia. Cancer Genet Cytogenet 138:89–91PubMedCrossRef
20.
Zurück zum Zitat van Baren N, Brasseur F, Godelaine D et al (1999) Genes encoding tumour-specific antigens are expressed in human myeloma cells. Blood 94:1156–1164PubMed van Baren N, Brasseur F, Godelaine D et al (1999) Genes encoding tumour-specific antigens are expressed in human myeloma cells. Blood 94:1156–1164PubMed
21.
Zurück zum Zitat Matsushita M, Ikeda H, Kizaki M et al (2001) Quantitative monitoring of the PRAME gene for the detection of minimal residual disease in leukaemia. Br J Haematol 112:916–926PubMedCrossRef Matsushita M, Ikeda H, Kizaki M et al (2001) Quantitative monitoring of the PRAME gene for the detection of minimal residual disease in leukaemia. Br J Haematol 112:916–926PubMedCrossRef
Metadaten
Titel
Prevalence and prognostic and predictive relevance of PRAME in breast cancer
verfasst von
Padraig Doolan
Martin Clynes
Susan Kennedy
Jai Prakash Mehta
John Crown
Lorraine O’Driscoll
Publikationsdatum
01.05.2008
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 2/2008
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-007-9643-3

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