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Erschienen in: Breast Cancer Research and Treatment 2/2013

01.04.2013 | Clinical trial

Disseminated tumour cells in the bone marrow in early breast cancer: morphological categories of immunocytochemically positive cells have different impact on clinical outcome

verfasst von: M. Synnestvedt, E. Borgen, E. Schlichting, C. B. Schirmer, A. Renolen, K. E. Giercksky, J. M. Nesland, B. Naume

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2013

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Abstract

Detection of disseminated tumour cells (DTCs) in bone marrow by immunocytochemistry (ICC) includes morphological evaluation of cytokeratin immunopositive cells. The aim of this study was to disclose the prognostic significance of different morphological categories of ICC-positive cells according to treatment status and tumour subtype. Bone marrow samples (at surgery) were analysed for the presence of cytokeratin-positive DTCs by a standard immunocytochemical method. The immunopositive cells were classified into the following categories, prior to any analysis of the association between DTCs and clinical outcome: tumour cells (TC), uninterpretable cells (UIC), hematopoietic cells (HC), and questionable HC (QHC). The analysis included 747 early breast cancer patients. Median follow-up was 84 months for relapse, and 99 months for death. The categorisation of the ICC positive cells revealed TC in 13.3 % of the patients, whereas 13.1, 17.8, and 21.4 % of the cases were positive for UIC, QHC, and HC, respectively. Analysing all patients, only TC and UIC predicted systemic relapse. Separate analysis of all patients not receiving adjuvant systemic treatment (No-Adj; n = 389) showed that only QHC were associated with reduced survival (DDFS: p = 0.008; BCSS: p = 0.004, log rank) and the presence of QHC also remained significant in multivariate analysis. Primary tumour subgroup analysis (of all patients) by hormone receptors (HR) and HER2, demonstrated that only TC/UIC had prognostic impact in the HR+/HER2− patients, whereas presence of QHC was associated with unfavourable outcome only in triple negative patients (DDFS: p = 0.004; BCSS: p = 0.024). Patients with ≥3HC had improved outcome compared to those with fewer/no HC (DDFS: p = 0.005; BCSS: p = 0.009). Hence, morphological DTC subgroups may differ in clinical significance according to primary tumour subtype and treatment status. This emphasises the importance of DTC characterisation, and separate analyses of DTC categories according to tumour subtype. Hematopoietic (“false positive”) cells might predict an immune-related favorable clinical outcome.
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Literatur
1.
Zurück zum Zitat Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC, Schlimok G, Diel IJ, Gerber B, Gebauer G, Pierga JY, Marth C, Oruzio D, Wiedswang G, Solomayer EF, Kundt G, Strobl B, Fehm T, Wong GY, Bliss J, Vincent-Salomon A, Pantel K (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353:793–802PubMedCrossRef Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC, Schlimok G, Diel IJ, Gerber B, Gebauer G, Pierga JY, Marth C, Oruzio D, Wiedswang G, Solomayer EF, Kundt G, Strobl B, Fehm T, Wong GY, Bliss J, Vincent-Salomon A, Pantel K (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353:793–802PubMedCrossRef
2.
Zurück zum Zitat Janni W, Vogl FD, Wiedswang G, Synnestvedt M, Fehm T, Juckstock J, Borgen E, Rack B, Braun S, Sommer H, Solomayer E, Pantel K, Nesland J, Friese K, Naume B (2011) Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse–a European pooled analysis. Clin Cancer Res 17:2967–2976PubMedCrossRef Janni W, Vogl FD, Wiedswang G, Synnestvedt M, Fehm T, Juckstock J, Borgen E, Rack B, Braun S, Sommer H, Solomayer E, Pantel K, Nesland J, Friese K, Naume B (2011) Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse–a European pooled analysis. Clin Cancer Res 17:2967–2976PubMedCrossRef
3.
Zurück zum Zitat Borgen E, Naume B, Nesland JM, Kvalheim G, Beiske K, Fodstad O, Diel I, Solomayer EF, Theocharous P, Coombes RC, Smith BM, Wunder E, Marolleau JP, Garcia J, Pantel K (1999) Standardization of the immunocytochemical detection of cancer cells in BM and blood: I. Establishment of objective criteria for the evaluation of immunostained cells. Cytotherapy 1:377–388PubMedCrossRef Borgen E, Naume B, Nesland JM, Kvalheim G, Beiske K, Fodstad O, Diel I, Solomayer EF, Theocharous P, Coombes RC, Smith BM, Wunder E, Marolleau JP, Garcia J, Pantel K (1999) Standardization of the immunocytochemical detection of cancer cells in BM and blood: I. Establishment of objective criteria for the evaluation of immunostained cells. Cytotherapy 1:377–388PubMedCrossRef
4.
Zurück zum Zitat Fehm T, Braun S, Muller V, Janni W, Gebauer G, Marth C, Schindlbeck C, Wallwiener D, Borgen E, Naume B, Pantel K, Solomayer E (2006) A concept for the standardized detection of disseminated tumor cells in bone marrow from patients with primary breast cancer and its clinical implementation. Cancer 107:885–892PubMedCrossRef Fehm T, Braun S, Muller V, Janni W, Gebauer G, Marth C, Schindlbeck C, Wallwiener D, Borgen E, Naume B, Pantel K, Solomayer E (2006) A concept for the standardized detection of disseminated tumor cells in bone marrow from patients with primary breast cancer and its clinical implementation. Cancer 107:885–892PubMedCrossRef
5.
Zurück zum Zitat Bidard FC, Vincent-Salomon A, Gomme S, Nos C, de Rycke Y, Thiery JP, Sigal-Zafrani B, Mignot L, Sastre-Garau X, Pierga JY (2008) Disseminated tumor cells of breast cancer patients: a strong prognostic factor for distant and local relapse. Clin Cancer Res 14:3306–3311PubMedCrossRef Bidard FC, Vincent-Salomon A, Gomme S, Nos C, de Rycke Y, Thiery JP, Sigal-Zafrani B, Mignot L, Sastre-Garau X, Pierga JY (2008) Disseminated tumor cells of breast cancer patients: a strong prognostic factor for distant and local relapse. Clin Cancer Res 14:3306–3311PubMedCrossRef
6.
Zurück zum Zitat Naume B, Wiedswang G, Borgen E, Kvalheim G, Karesen R, Qvist H, Janbu J, Harbitz T, Nesland JM (2004) The prognostic value of isolated tumor cells in bone marrow in breast cancer patients: evaluation of morphological categories and the number of clinically significant cells. Clin Cancer Res 10:3091–3097PubMedCrossRef Naume B, Wiedswang G, Borgen E, Kvalheim G, Karesen R, Qvist H, Janbu J, Harbitz T, Nesland JM (2004) The prognostic value of isolated tumor cells in bone marrow in breast cancer patients: evaluation of morphological categories and the number of clinically significant cells. Clin Cancer Res 10:3091–3097PubMedCrossRef
7.
Zurück zum Zitat Naume B, Borgen E, Kvalheim G, Karesen R, Qvist H, Sauer T, Kumar T, Nesland JM (2001) Detection of isolated tumor cells in bone marrow in early-stage breast carcinoma patients: comparison with preoperative clinical parameters and primary tumor characteristics. Clin Cancer Res 7:4122–4129PubMed Naume B, Borgen E, Kvalheim G, Karesen R, Qvist H, Sauer T, Kumar T, Nesland JM (2001) Detection of isolated tumor cells in bone marrow in early-stage breast carcinoma patients: comparison with preoperative clinical parameters and primary tumor characteristics. Clin Cancer Res 7:4122–4129PubMed
8.
Zurück zum Zitat Wiedswang G, Borgen E, Karesen R, Kvalheim G, Nesland JM, Qvist H, Schlichting E, Sauer T, Janbu J, Harbitz T, Naume B (2003) Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer. J Clin Oncol 21:3469–3478PubMedCrossRef Wiedswang G, Borgen E, Karesen R, Kvalheim G, Nesland JM, Qvist H, Schlichting E, Sauer T, Janbu J, Harbitz T, Naume B (2003) Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer. J Clin Oncol 21:3469–3478PubMedCrossRef
9.
Zurück zum Zitat Wiedswang G, Borgen E, Karesen R, Qvist H, Janbu J, Kvalheim G, Nesland JM, Naume B (2004) Isolated tumor cells in bone marrow three years after diagnosis in disease-free breast cancer patients predict unfavorable clinical outcome. Clin Cancer Res 10:5342–5348PubMedCrossRef Wiedswang G, Borgen E, Karesen R, Qvist H, Janbu J, Kvalheim G, Nesland JM, Naume B (2004) Isolated tumor cells in bone marrow three years after diagnosis in disease-free breast cancer patients predict unfavorable clinical outcome. Clin Cancer Res 10:5342–5348PubMedCrossRef
10.
Zurück zum Zitat Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y, Graf S, Ha G, Haffari G, Bashashati A, Russell R, McKinney S, Langerod A, Green A, Provenzano E, Wishart G, Pinder S, Watson P, Markowetz F, Murphy L, Ellis I et al (2012) The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486:346–352PubMed Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y, Graf S, Ha G, Haffari G, Bashashati A, Russell R, McKinney S, Langerod A, Green A, Provenzano E, Wishart G, Pinder S, Watson P, Markowetz F, Murphy L, Ellis I et al (2012) The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486:346–352PubMed
11.
Zurück zum Zitat Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ (2011) Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22:1736–1747PubMedCrossRef Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ (2011) Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22:1736–1747PubMedCrossRef
12.
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 19:403–410PubMedCrossRef 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 19:403–410PubMedCrossRef
13.
Zurück zum Zitat 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 d V, 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 131:18–43PubMed 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 d V, 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 131:18–43PubMed
14.
Zurück zum Zitat Cordell JL, Falini B, Erber WN, Ghosh AK, Abdulaziz Z, MacDonald S, Pulford KA, Stein H, Mason DY (1984) Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 32:219–229PubMedCrossRef Cordell JL, Falini B, Erber WN, Ghosh AK, Abdulaziz Z, MacDonald S, Pulford KA, Stein H, Mason DY (1984) Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 32:219–229PubMedCrossRef
15.
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 100:229–235PubMedCrossRef 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 100:229–235PubMedCrossRef
16.
Zurück zum Zitat Kraan J, Sleijfer S, Strijbos MH, Ignatiadis M, Peeters D, Pierga JY, Farace F, Riethdorf S, Fehm T, Zorzino L, Tibbe AG, Maestro M, Gisbert-Criado R, Denton G, de Bono JS, Dive C, Foekens JA, Gratama JW (2011) External quality assurance of circulating tumor cell enumeration using the Cell Search® system: a feasibility study. Cytometry B Clin Cytom 80:112–118PubMed Kraan J, Sleijfer S, Strijbos MH, Ignatiadis M, Peeters D, Pierga JY, Farace F, Riethdorf S, Fehm T, Zorzino L, Tibbe AG, Maestro M, Gisbert-Criado R, Denton G, de Bono JS, Dive C, Foekens JA, Gratama JW (2011) External quality assurance of circulating tumor cell enumeration using the Cell Search® system: a feasibility study. Cytometry B Clin Cytom 80:112–118PubMed
17.
Zurück zum Zitat Borgen E, Pantel K, Schlimok G, Muller P, Otte M, Renolen A, Ehnle S, Coith C, Nesland JM, Naume B (2006) A European interlaboratory testing of three well-known procedures for immunocytochemical detection of epithelial cells in bone marrow. Results from analysis of normal bone marrow. Cytom B Clin Cytom 70:400–409CrossRef Borgen E, Pantel K, Schlimok G, Muller P, Otte M, Renolen A, Ehnle S, Coith C, Nesland JM, Naume B (2006) A European interlaboratory testing of three well-known procedures for immunocytochemical detection of epithelial cells in bone marrow. Results from analysis of normal bone marrow. Cytom B Clin Cytom 70:400–409CrossRef
18.
Zurück zum Zitat Krag DN, Kusminsky R, Manna E, Weaver D, Harlow SP, Covelli M, Stanley MA, McCahill L, Ittleman F, Leavitt B, Krag M, Amarante P (2009) Cytokeratin-positive cells in the bone marrow of breast cancer patients and noncancer donors. Appl Immunohistochem Mol Morphol 17:403–408PubMedCrossRef Krag DN, Kusminsky R, Manna E, Weaver D, Harlow SP, Covelli M, Stanley MA, McCahill L, Ittleman F, Leavitt B, Krag M, Amarante P (2009) Cytokeratin-positive cells in the bone marrow of breast cancer patients and noncancer donors. Appl Immunohistochem Mol Morphol 17:403–408PubMedCrossRef
19.
Zurück zum Zitat Coumans FA, Doggen CJ, Attard G, de Bono JS, Terstappen LW (2010) All circulating EpCAM+ CK+. Ann Oncol 21:1851–1857PubMedCrossRef Coumans FA, Doggen CJ, Attard G, de Bono JS, Terstappen LW (2010) All circulating EpCAM+ CK+. Ann Oncol 21:1851–1857PubMedCrossRef
20.
Zurück zum Zitat Kim C, Paik S (2010) Gene-expression-based prognostic assays for breast cancer. Nat Rev Clin Oncol 7:340–347PubMedCrossRef Kim C, Paik S (2010) Gene-expression-based prognostic assays for breast cancer. Nat Rev Clin Oncol 7:340–347PubMedCrossRef
21.
22.
Zurück zum Zitat Meng S, Tripathy D, Frenkel EP, Shete S, Naftalis EZ, Huth JF, Beitsch PD, Leitch M, Hoover S, Euhus D, Haley B, Morrison L, Fleming TP, Herlyn D, Terstappen LW, Fehm T, Tucker TF, Lane N, Wang J, Uhr JW (2004) Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 10:8152–8162PubMedCrossRef Meng S, Tripathy D, Frenkel EP, Shete S, Naftalis EZ, Huth JF, Beitsch PD, Leitch M, Hoover S, Euhus D, Haley B, Morrison L, Fleming TP, Herlyn D, Terstappen LW, Fehm T, Tucker TF, Lane N, Wang J, Uhr JW (2004) Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 10:8152–8162PubMedCrossRef
23.
Zurück zum Zitat Jordan NV, Johnson GL, Abell AN (2011) Tracking the intermediate stages of epithelial-mesenchymal transition in epithelial stem cells and cancer. Cell Cycle 10:2865–2873PubMedCrossRef Jordan NV, Johnson GL, Abell AN (2011) Tracking the intermediate stages of epithelial-mesenchymal transition in epithelial stem cells and cancer. Cell Cycle 10:2865–2873PubMedCrossRef
24.
Zurück zum Zitat Hall C, Krishnamurthy S, Lodhi A, Mosalpuria K, Kuerer HM, Meric-Bernstam F, Bedrosian I, Hunt KK, Lucci A (2010) Disseminated tumor cells in biologic subtypes of stage I–III breast cancer patients. Ann Surg Oncol 17:3252–3258PubMedCrossRef Hall C, Krishnamurthy S, Lodhi A, Mosalpuria K, Kuerer HM, Meric-Bernstam F, Bedrosian I, Hunt KK, Lucci A (2010) Disseminated tumor cells in biologic subtypes of stage I–III breast cancer patients. Ann Surg Oncol 17:3252–3258PubMedCrossRef
25.
Zurück zum Zitat von Minckwitz G, Martin M (2012) Neoadjuvant treatments for triple-negative breast cancer (TNBC). Ann Oncol 23 Suppl 6:vi35–vi39CrossRef von Minckwitz G, Martin M (2012) Neoadjuvant treatments for triple-negative breast cancer (TNBC). Ann Oncol 23 Suppl 6:vi35–vi39CrossRef
26.
Zurück zum Zitat Borgen E, Beiske K, Trachsel S, Nesland JM, Kvalheim G, Herstad TK, Schlichting E, Qvist H, Naume B (1998) Immunocytochemical detection of isolated epithelial cells in bone marrow: non-specific staining and contribution by plasma cells directly reactive to alkaline phosphatase. J Pathol 185:427–434PubMedCrossRef Borgen E, Beiske K, Trachsel S, Nesland JM, Kvalheim G, Herstad TK, Schlichting E, Qvist H, Naume B (1998) Immunocytochemical detection of isolated epithelial cells in bone marrow: non-specific staining and contribution by plasma cells directly reactive to alkaline phosphatase. J Pathol 185:427–434PubMedCrossRef
27.
Zurück zum Zitat Schmidt M, Hellwig B, Hammad S, Othman A, Lohr M, Chen Z, Boehm D, Gebhard S, Petry I, Lebrecht A, Cadenas C, Marchan R, Stewart JD, Solbach C, Holmberg L, Edlund K, Kultima HG, Rody A et al (2012) A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin kappa C as a compatible prognostic marker in human solid tumors. Clin Cancer Res 18:2695–2703PubMedCrossRef Schmidt M, Hellwig B, Hammad S, Othman A, Lohr M, Chen Z, Boehm D, Gebhard S, Petry I, Lebrecht A, Cadenas C, Marchan R, Stewart JD, Solbach C, Holmberg L, Edlund K, Kultima HG, Rody A et al (2012) A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin kappa C as a compatible prognostic marker in human solid tumors. Clin Cancer Res 18:2695–2703PubMedCrossRef
28.
Zurück zum Zitat Blankenstein T, Coulie PG, Gilboa E, Jaffee EM (2012) The determinants of tumour immunogenicity. Nat Rev Cancer 12:307–313PubMedCrossRef Blankenstein T, Coulie PG, Gilboa E, Jaffee EM (2012) The determinants of tumour immunogenicity. Nat Rev Cancer 12:307–313PubMedCrossRef
29.
Zurück zum Zitat Kristensen VN, Vaske CJ, Ursini-Siegel J, Van LP, Nordgard SH, Sachidanandam R, Sorlie T, Warnberg F, Haakensen VD, Helland A, Naume B, Perou CM, Haussler D, Troyanskaya OG, Borresen-Dale AL (2012) Integrated molecular profiles of invasive breast tumors and ductal carcinoma in situ (DCIS) reveal differential vascular and interleukin signaling. Proc Natl Acad Sci USA 109:2802–2807PubMedCrossRef Kristensen VN, Vaske CJ, Ursini-Siegel J, Van LP, Nordgard SH, Sachidanandam R, Sorlie T, Warnberg F, Haakensen VD, Helland A, Naume B, Perou CM, Haussler D, Troyanskaya OG, Borresen-Dale AL (2012) Integrated molecular profiles of invasive breast tumors and ductal carcinoma in situ (DCIS) reveal differential vascular and interleukin signaling. Proc Natl Acad Sci USA 109:2802–2807PubMedCrossRef
30.
Zurück zum Zitat Stevens KN, Fredericksen Z, Vachon CM, Wang X, Margolin S, Lindblom A, Nevanlinna H, Greco D, Aittomaki K, Blomqvist C, Chang-Claude J, Vrieling A, Flesch-Janys D, Sinn HP, Wang-Gohrke S, Nickels S, Brauch H, Ko YD, Fischer HP, Schmutzler RK, Meindl A, Bartram CR, Schott S, Engel C, Godwin AK et al (2012) 19p13.1 is a triple-negative-specific breast cancer susceptibility locus. Cancer Res 72:1795–1803PubMedCrossRef Stevens KN, Fredericksen Z, Vachon CM, Wang X, Margolin S, Lindblom A, Nevanlinna H, Greco D, Aittomaki K, Blomqvist C, Chang-Claude J, Vrieling A, Flesch-Janys D, Sinn HP, Wang-Gohrke S, Nickels S, Brauch H, Ko YD, Fischer HP, Schmutzler RK, Meindl A, Bartram CR, Schott S, Engel C, Godwin AK et al (2012) 19p13.1 is a triple-negative-specific breast cancer susceptibility locus. Cancer Res 72:1795–1803PubMedCrossRef
31.
Zurück zum Zitat DeNardo DG, Coussens LM (2007) Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression. Breast Cancer Res 9:212PubMedCrossRef DeNardo DG, Coussens LM (2007) Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression. Breast Cancer Res 9:212PubMedCrossRef
32.
Zurück zum Zitat Balic M, Rapp N, Stanzer S, Lin H, Strutz J, Szkandera J, Daidone MG, Samonigg H, Cote RJ, Dandachi N (2011) Novel immunofluorescence protocol for multimarker assessment of putative disseminating breast cancer stem cells. Appl Immunohistochem Mol Morphol 19:33–40PubMedCrossRef Balic M, Rapp N, Stanzer S, Lin H, Strutz J, Szkandera J, Daidone MG, Samonigg H, Cote RJ, Dandachi N (2011) Novel immunofluorescence protocol for multimarker assessment of putative disseminating breast cancer stem cells. Appl Immunohistochem Mol Morphol 19:33–40PubMedCrossRef
33.
Zurück zum Zitat Fehm T, Muller V, Alix-Panabieres C, Pantel K (2008) Micrometastatic spread in breast cancer: detection, molecular characterization and clinical relevance. Breast Cancer Res 10(Suppl 1):S1PubMedCrossRef Fehm T, Muller V, Alix-Panabieres C, Pantel K (2008) Micrometastatic spread in breast cancer: detection, molecular characterization and clinical relevance. Breast Cancer Res 10(Suppl 1):S1PubMedCrossRef
34.
Zurück zum Zitat Mathiesen RR, Fjelldal R, Liestol K, Due EU, Geigl JB, Riethdorf S, Borgen E, Rye IH, Schneider IJ, Obenauf AC, Mauermann O, Nilsen G, Christian LO, Borresen-Dale AL, Pantel K, Speicher MR, Naume B, Baumbusch LO (2011) High-resolution analyses of copy number changes in disseminated tumor cells of patients with breast cancer. Int J Cancer 131:E405–E415 Mathiesen RR, Fjelldal R, Liestol K, Due EU, Geigl JB, Riethdorf S, Borgen E, Rye IH, Schneider IJ, Obenauf AC, Mauermann O, Nilsen G, Christian LO, Borresen-Dale AL, Pantel K, Speicher MR, Naume B, Baumbusch LO (2011) High-resolution analyses of copy number changes in disseminated tumor cells of patients with breast cancer. Int J Cancer 131:E405–E415
35.
Zurück zum Zitat Riethdorf S, Pantel K (2008) Disseminated tumor cells in bone marrow and circulating tumor cells in blood of breast cancer patients: current state of detection and characterization. Pathobiology 75:140–148PubMedCrossRef Riethdorf S, Pantel K (2008) Disseminated tumor cells in bone marrow and circulating tumor cells in blood of breast cancer patients: current state of detection and characterization. Pathobiology 75:140–148PubMedCrossRef
36.
Zurück zum Zitat Pierga JY, Bonneton C, Magdelenat H, Vincent-Salomon A, Nos C, Boudou E, Pouillart P, Thiery JP, de CP (2005) Real-time quantitative PCR determination of urokinase-type plasminogen activator receptor (uPAR) expression of isolated micrometastatic cells from bone marrow of breast cancer patients. Int J Cancer 114:291–298PubMedCrossRef Pierga JY, Bonneton C, Magdelenat H, Vincent-Salomon A, Nos C, Boudou E, Pouillart P, Thiery JP, de CP (2005) Real-time quantitative PCR determination of urokinase-type plasminogen activator receptor (uPAR) expression of isolated micrometastatic cells from bone marrow of breast cancer patients. Int J Cancer 114:291–298PubMedCrossRef
37.
Zurück zum Zitat Fehm T, Solomayer EF, Meng S, Tucker T, Lane N, Wang J, Gebauer G (2005) Methods for isolating circulating epithelial cells and criteria for their classification as carcinoma cells. Cytotherapy 7:171–185PubMedCrossRef Fehm T, Solomayer EF, Meng S, Tucker T, Lane N, Wang J, Gebauer G (2005) Methods for isolating circulating epithelial cells and criteria for their classification as carcinoma cells. Cytotherapy 7:171–185PubMedCrossRef
38.
Zurück zum Zitat Payne RE, Wang F, Su N, Krell J, Zebrowski A, Yague E, Ma XJ, Luo Y, Coombes RC (2012) Viable circulating tumour cell detection using multiplex RNA in situ hybridisation predicts progression-free survival in metastatic breast cancer patients. Br J Cancer 106:1790–1797PubMedCrossRef Payne RE, Wang F, Su N, Krell J, Zebrowski A, Yague E, Ma XJ, Luo Y, Coombes RC (2012) Viable circulating tumour cell detection using multiplex RNA in situ hybridisation predicts progression-free survival in metastatic breast cancer patients. Br J Cancer 106:1790–1797PubMedCrossRef
39.
Zurück zum Zitat Bidard FC, Vincent-Salomon A, Sigal-Zafrani B, Dieras V, Mathiot C, Mignot L, Thiery JP, Sastre-Garau X, Pierga JY (2008) Prognosis of women with stage IV breast cancer depends on detection of circulating tumor cells rather than disseminated tumor cells. Ann Oncol 19:496–500PubMedCrossRef Bidard FC, Vincent-Salomon A, Sigal-Zafrani B, Dieras V, Mathiot C, Mignot L, Thiery JP, Sastre-Garau X, Pierga JY (2008) Prognosis of women with stage IV breast cancer depends on detection of circulating tumor cells rather than disseminated tumor cells. Ann Oncol 19:496–500PubMedCrossRef
40.
Zurück zum Zitat Pierga JY, Bonneton C, Vincent-Salomon A, de CP, Nos C, Blin N, Pouillart P, Thiery JP, Magdelenat H (2004) Clinical significance of immunocytochemical detection of tumor cells using digital microscopy in peripheral blood and bone marrow of breast cancer patients. Clin Cancer Res 10:1392–1400PubMedCrossRef Pierga JY, Bonneton C, Vincent-Salomon A, de CP, Nos C, Blin N, Pouillart P, Thiery JP, Magdelenat H (2004) Clinical significance of immunocytochemical detection of tumor cells using digital microscopy in peripheral blood and bone marrow of breast cancer patients. Clin Cancer Res 10:1392–1400PubMedCrossRef
41.
Zurück zum Zitat Molloy TJ, Bosma AJ, Baumbusch LO, Synnestvedt M, Borgen E, Russnes HG, Schlichting E, van’t Veer LJ, Naume B (2011) The prognostic significance of tumour cell detection in the peripheral blood versus the bone marrow in 733 early-stage breast cancer patients. Breast Cancer Res 13:R61PubMedCrossRef Molloy TJ, Bosma AJ, Baumbusch LO, Synnestvedt M, Borgen E, Russnes HG, Schlichting E, van’t Veer LJ, Naume B (2011) The prognostic significance of tumour cell detection in the peripheral blood versus the bone marrow in 733 early-stage breast cancer patients. Breast Cancer Res 13:R61PubMedCrossRef
42.
Zurück zum Zitat Ignatiadis M, Perraki M, Apostolaki S, Politaki E, Xenidis N, Kafousi M, Stathopoulos E, Lianidou E, Sotiriou C, Georgoulias V, Mavroudis D (2007) Molecular detection and prognostic value of circulating cytokeratin-19 messenger RNA-positive and HER2 messenger RNA-positive cells in the peripheral blood of women with early-stage breast cancer. Clin Breast Cancer 7:883–889PubMedCrossRef Ignatiadis M, Perraki M, Apostolaki S, Politaki E, Xenidis N, Kafousi M, Stathopoulos E, Lianidou E, Sotiriou C, Georgoulias V, Mavroudis D (2007) Molecular detection and prognostic value of circulating cytokeratin-19 messenger RNA-positive and HER2 messenger RNA-positive cells in the peripheral blood of women with early-stage breast cancer. Clin Breast Cancer 7:883–889PubMedCrossRef
43.
Zurück zum Zitat Molloy TJ, Roepman P, Naume B, van’t Veer LJ (2012) A prognostic gene expression profile that predicts circulating tumor cell presence in breast cancer patients. PLoS ONE 7:e32426PubMedCrossRef Molloy TJ, Roepman P, Naume B, van’t Veer LJ (2012) A prognostic gene expression profile that predicts circulating tumor cell presence in breast cancer patients. PLoS ONE 7:e32426PubMedCrossRef
44.
Zurück zum Zitat Naume B, Zhao X, Synnestvedt M, Borgen E, Russnes HG, Lingjaerde OC, Stromberg M, Wiedswang G, Kvalheim G, Karesen R, Nesland JM, Borresen-Dale AL, Sorlie T (2007) Presence of bone marrow micrometastasis is associated with different recurrence risk within molecular subtypes of breast cancer. Mol Oncol 1:160–171PubMedCrossRef Naume B, Zhao X, Synnestvedt M, Borgen E, Russnes HG, Lingjaerde OC, Stromberg M, Wiedswang G, Kvalheim G, Karesen R, Nesland JM, Borresen-Dale AL, Sorlie T (2007) Presence of bone marrow micrometastasis is associated with different recurrence risk within molecular subtypes of breast cancer. Mol Oncol 1:160–171PubMedCrossRef
45.
Zurück zum Zitat Woelfle U, Cloos J, Sauter G, Riethdorf L, Janicke F, van Diest P, Brakenhoff R, Pantel K (2003) Molecular signature associated with bone marrow micrometastasis in human breast cancer. Cancer Res 63:5679–5684PubMed Woelfle U, Cloos J, Sauter G, Riethdorf L, Janicke F, van Diest P, Brakenhoff R, Pantel K (2003) Molecular signature associated with bone marrow micrometastasis in human breast cancer. Cancer Res 63:5679–5684PubMed
Metadaten
Titel
Disseminated tumour cells in the bone marrow in early breast cancer: morphological categories of immunocytochemically positive cells have different impact on clinical outcome
verfasst von
M. Synnestvedt
E. Borgen
E. Schlichting
C. B. Schirmer
A. Renolen
K. E. Giercksky
J. M. Nesland
B. Naume
Publikationsdatum
01.04.2013
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 2/2013
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-013-2439-8

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