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Bone Marrow Micrometastasis Detected by Flow Cytometry is Associated Bone, Bone Marrow, Lung Macrometastasis in Breast Cancer

Year 2014, Volume: 39 Issue: 2, 305 - 314, 22.07.2014
https://doi.org/10.17826/cutf.38648

Abstract

Purpose: The aim of the present study was to analyze deposits in bone marrow for determining micrometastases in breast cancer patients by flow cytometry. And its correlation of prognostic factors and macrometastasis at the first diagnosis. Material and Methods: Bone marrow samples were obtained from 52 breast cancer patients and 16 control patients via aspiration from the iliac spine at the time of first diagnosis after the surgery. Epithelial cells were identified with anti-cytokeratin monoclonal antibody, and double-staining with propidium iodide and CD45using flow cytometry. Results: In all, 2 (12.5%) of the 16 control patients and 11 (21%) of the 52 breast cancer patients had cytokeratin-18 positive cells in their bone marrow. A relationship between the presence of occult metastatic cells in bone marrow, and the presence/absence of lymph node metastases, tumor size, stage, menopausal status, hormone receptor status, histological grade, c-erb-B2 expression, tumor subtype, lymphovascular invasion, Ductal carcinoma in situ (DCIS) component, and gender was not observed. Significant positive relationships were observed between bone marrow micrometastasis, and age, and bone, bone marrow, lung, and liver metastases. Conclusion: Bone marrow micrometastasis was associated with age, bone, bone marrow, lung, and liver metastases at the time of diagnosis..

References

  • Balic M, Williams A, Dandachi N, Cote RJ. Micrometastasis: detection methods and clinical importance. Cancer Biomark. 2011;9:397-419.
  • Pantel K, Alix-Panabières C, Riethdorf S. Cancer micrometastases.Nat Rev Clin Oncol. 2009;6:339-51.
  • Mansi JL, Gogas H, Bliss JM. Outcome of primarybreast-cancer patients with micrometastases: a longterm follow-up study. Lancet 1999;354:197-202.
  • Diel IJ, Kaufmann M, Costa SD. Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status. J Natl Cancer Inst. 1996;88:1652-658.
  • Braun S, Kentenich C, Janni W. Lack of effect of adjuvant chemotherapy on the elimination of single dormant tumor cells in bone marrow of high-risk breast cancer patients. J Clin Oncol 2000;18:80-6.
  • Diel IJ, Solomayer EF, Costa SD. Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engl J Med. 1998;339:357-63.
  • Pantel K, Schlimok G, Angstwurm M, et al. Methodological analysis of immunocytochemical screening for disseminated epithelial tumor cells in bone marrow. J Hematother. 1994;3:165-73.
  • O’Sullivan GC, Collins JK, O’Brien F, et al. Micrometastases in bone marrow of patients undergoing curative surgery for gastrointestinal cancer. Gastroenterology. 1995;109:1535-40.
  • Molino A, Colombatti M, Bonetti F, et al. A comparative analysis of three different techniques for the detection of breast cancer cells in bone marrow. Cancer. 1991;67:1033-6.
  • Pantel K, Woelfle U. Cancer micrometastasis: Detection, clinical relevance, and molecular description. In: ASCO educational book, Lisa Graves Publisher, USA, 2004;701-08.
  • Zhu L, Lam CK, Chow LWC. Sentinel lymph node biopsy or detection of micrometastasis in bone marrow: Which might be an alternative to axillary lymph node dissection in breast cancer patients? Asian Journal of Surgery. 2004;27:279-83.
  • Dearnaley D P, Sloane JP, Ormerod MG, Steele K, Coombes RC, Clink HM. Increased detection of mammary carcinoma cells in marrow smears using antisera to epithelial membrane antigen. British Journal of Cancer. 1981;44:85-90.
  • Timar J, Csuka O, Orosz Z, Jeney A, Kopper L. Molecular pathology of tumor metastasis: II. Molecular staging and differential diagnosis. Pathology Oncology Research. 2002;8:204-19.
  • Guinebretiere JM, Contesso G. “Micrometastases”: The pathologist’s point of view. Bulletin du Cancer. 2001;88:549-50, 555-60.
  • Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med. 2005;353: 793-802.
  • Braun S, Pantel K, Muller P. Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. N Engl J Med. 2000;342:525-33.
  • Harbeck N. Tumour cell detection in the bone marrow of breast cancer patients at primary therapy: results of a 3-year median follow-up. Br J Cancer 1991;69:566–71.
  • Benoy IH, Elst H, Philips M. Prognostic significance of disseminated tumor cells as detected by quantitative real-time reverse-transcriptase polymerase chain reaction in patients with breast cancer. Clinical Breast Cancer. 2006;7(2):146-52.
  • Masuda TA, Kataoka A, Ohno S, et al. Detection of occult cancer cells in peripheral blood and bone marrow by quantitative RT-PCR assay for cytokeratin-7 in breast cancer patients. International Journal of Oncology. 2005;26:721–30.
  • Gebauer G, Fehm T. Micrometastases in axillary lymph nodes and bone marrow of lymph nodenegative breast cancer patients: Prognostic relevance after 10 years. Anticancer Research. 2003;23:4319-24.
  • Landys K, Persson S, Kovarik J, Hultborn R, Holmberg E. Prognostic value of bone marrow biopsy in operable breast cancer patients at the time of initial diagnosis: results of a 20-year median follow-up. Breast Cancer Res Treat. 1998;49:27-33.
  • Funke I, Fries S, Rolle M. Comparative analyses of bone marrow micrometastases in breast and gastric cancer. Int J Cancer. 1996;65:755-61.
  • Pierga JY, Bonneton C, Magdelenat H, et al. Realtime quantitative PCR determination of urokinasetype plasminogen activator receptor (uPAR) expression of isolated micrometastatic cells from bone marrow of breast cancer patients. Int J Cancer 2005;114:291-98.
  • Emens LA, Reilly RT, Jaffee EM. Breast Cancer vaccines: maximizing cancer treatment by tapping into host immunity. Endocrine-Related Cancer. 2005;12:1–17.
  • Bidard F, Vincent-Salomon A, Sigal-Zafrani B, et al. Prognosis of women with Stage IV breast cancer depends on detection of circulating tumor cells rather than disseminated tumor cells. Annals of Oncology. 2008;19(3):496-500.
  • Naume B, Borgen E, Kvalheim G, et al. 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. 2001;7:4122-29.
  • Jung YS, Lee KJ. Clinical Significance of Bone Marrow Micrometastasis Detected by Nested RTPCR for Keratin-19 in Breast Cancer Patients. Jpn J Clin Oncol. 2003;33:167–72.
  • Donegan WL. Tumor-Related Prognostic Factors for Breast Cancer CA Cancer J Clin. 1997;47:28-51.
  • Magire D, O’Sullivan GC, McNamara B. Bone marrow micrometastases in patient with brain metastases from epithelial cell tumours. Q J Med. 2000;93:611-15.
  • Yazışma Adresi / Address for Correspondence: Dr. Berna Bozkurt Duman Cukurova University Faculty of Medicine Department of Medical Oncology Tel:+90322 338 60 60 Fax :+90322 338 70 10
  • E-mail: berboz@hotmail.com geliş tarihi/received :11.11.2013 kabul tarihi/accepted:09.12.2013

Göğüs Kanserinde Flow Sitometri ile Tespit Edilenen Kemik İliği Mikrometastazının Kemik, Kemik İliği, ve Akciğer Makrometastazları ile İlişkilidir

Year 2014, Volume: 39 Issue: 2, 305 - 314, 22.07.2014
https://doi.org/10.17826/cutf.38648

Abstract

Amaç: Bu çalışmanın amacı, flow sitometri ile göğüs kanseri hastalarında mikrometastazların belirlenmesi için kemik iliği analizi yapılması ve bulguların ilk tanıdaki prognostik faktorler ve makrometastazlar ile korelasyonur. Materyal ve Metod: Kemik iliği örnekleri 52 göğüs kanserli hasta grubu ve 16 kontrol grubunun iliyak omurundan aspirasyonla alındı. Epitel hücreleri flow sitometrisi kullanılarak propidyum iyodür ve CD45 ile birlikte anti-sitokeratin monoklonal antikor ve ikili boyama ile tanımlandı. Bulgular: Toplamda, 52 göğüs kanseri hastasının 11 (% 21)'inde ve 16 kontrol grubunun 2 (%12.5)'sinde kemik iliğinde sitokeratin 18-pozitif hücreleri vardı. Kemik iliğinde gizli metastatik hücrelerin varlığı, ve lenf nodu metastazının varlığı/yokluğu, tümörün boyutu, evresi, menopozal durumu, hormon reseptör durumu, histolojik derecesi, c-erb-B2 ifadesi, tümör altgrubu, lenfovasküler nöbet, Duktal karsinomanın tamamlayıcı bileşeni (DCIS), ve cinsiyet arasında bir ilişki gözlenmedi. Yaş, kemik, kemik iliği, akciğer ve karaciğer ile kemik iliği mikrometastazı arasında anlamlı pozitif bir ilişki olduğu gözlemlendi. Sonuç: Tanı sırasında yaş, kemik, kemik iliği, akciğer ve karaciğer metastazıyla kemik iliği mikrometastazları ilişkiledirildi.

References

  • Balic M, Williams A, Dandachi N, Cote RJ. Micrometastasis: detection methods and clinical importance. Cancer Biomark. 2011;9:397-419.
  • Pantel K, Alix-Panabières C, Riethdorf S. Cancer micrometastases.Nat Rev Clin Oncol. 2009;6:339-51.
  • Mansi JL, Gogas H, Bliss JM. Outcome of primarybreast-cancer patients with micrometastases: a longterm follow-up study. Lancet 1999;354:197-202.
  • Diel IJ, Kaufmann M, Costa SD. Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status. J Natl Cancer Inst. 1996;88:1652-658.
  • Braun S, Kentenich C, Janni W. Lack of effect of adjuvant chemotherapy on the elimination of single dormant tumor cells in bone marrow of high-risk breast cancer patients. J Clin Oncol 2000;18:80-6.
  • Diel IJ, Solomayer EF, Costa SD. Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engl J Med. 1998;339:357-63.
  • Pantel K, Schlimok G, Angstwurm M, et al. Methodological analysis of immunocytochemical screening for disseminated epithelial tumor cells in bone marrow. J Hematother. 1994;3:165-73.
  • O’Sullivan GC, Collins JK, O’Brien F, et al. Micrometastases in bone marrow of patients undergoing curative surgery for gastrointestinal cancer. Gastroenterology. 1995;109:1535-40.
  • Molino A, Colombatti M, Bonetti F, et al. A comparative analysis of three different techniques for the detection of breast cancer cells in bone marrow. Cancer. 1991;67:1033-6.
  • Pantel K, Woelfle U. Cancer micrometastasis: Detection, clinical relevance, and molecular description. In: ASCO educational book, Lisa Graves Publisher, USA, 2004;701-08.
  • Zhu L, Lam CK, Chow LWC. Sentinel lymph node biopsy or detection of micrometastasis in bone marrow: Which might be an alternative to axillary lymph node dissection in breast cancer patients? Asian Journal of Surgery. 2004;27:279-83.
  • Dearnaley D P, Sloane JP, Ormerod MG, Steele K, Coombes RC, Clink HM. Increased detection of mammary carcinoma cells in marrow smears using antisera to epithelial membrane antigen. British Journal of Cancer. 1981;44:85-90.
  • Timar J, Csuka O, Orosz Z, Jeney A, Kopper L. Molecular pathology of tumor metastasis: II. Molecular staging and differential diagnosis. Pathology Oncology Research. 2002;8:204-19.
  • Guinebretiere JM, Contesso G. “Micrometastases”: The pathologist’s point of view. Bulletin du Cancer. 2001;88:549-50, 555-60.
  • Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med. 2005;353: 793-802.
  • Braun S, Pantel K, Muller P. Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. N Engl J Med. 2000;342:525-33.
  • Harbeck N. Tumour cell detection in the bone marrow of breast cancer patients at primary therapy: results of a 3-year median follow-up. Br J Cancer 1991;69:566–71.
  • Benoy IH, Elst H, Philips M. Prognostic significance of disseminated tumor cells as detected by quantitative real-time reverse-transcriptase polymerase chain reaction in patients with breast cancer. Clinical Breast Cancer. 2006;7(2):146-52.
  • Masuda TA, Kataoka A, Ohno S, et al. Detection of occult cancer cells in peripheral blood and bone marrow by quantitative RT-PCR assay for cytokeratin-7 in breast cancer patients. International Journal of Oncology. 2005;26:721–30.
  • Gebauer G, Fehm T. Micrometastases in axillary lymph nodes and bone marrow of lymph nodenegative breast cancer patients: Prognostic relevance after 10 years. Anticancer Research. 2003;23:4319-24.
  • Landys K, Persson S, Kovarik J, Hultborn R, Holmberg E. Prognostic value of bone marrow biopsy in operable breast cancer patients at the time of initial diagnosis: results of a 20-year median follow-up. Breast Cancer Res Treat. 1998;49:27-33.
  • Funke I, Fries S, Rolle M. Comparative analyses of bone marrow micrometastases in breast and gastric cancer. Int J Cancer. 1996;65:755-61.
  • Pierga JY, Bonneton C, Magdelenat H, et al. Realtime quantitative PCR determination of urokinasetype plasminogen activator receptor (uPAR) expression of isolated micrometastatic cells from bone marrow of breast cancer patients. Int J Cancer 2005;114:291-98.
  • Emens LA, Reilly RT, Jaffee EM. Breast Cancer vaccines: maximizing cancer treatment by tapping into host immunity. Endocrine-Related Cancer. 2005;12:1–17.
  • Bidard F, Vincent-Salomon A, Sigal-Zafrani B, et al. Prognosis of women with Stage IV breast cancer depends on detection of circulating tumor cells rather than disseminated tumor cells. Annals of Oncology. 2008;19(3):496-500.
  • Naume B, Borgen E, Kvalheim G, et al. 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. 2001;7:4122-29.
  • Jung YS, Lee KJ. Clinical Significance of Bone Marrow Micrometastasis Detected by Nested RTPCR for Keratin-19 in Breast Cancer Patients. Jpn J Clin Oncol. 2003;33:167–72.
  • Donegan WL. Tumor-Related Prognostic Factors for Breast Cancer CA Cancer J Clin. 1997;47:28-51.
  • Magire D, O’Sullivan GC, McNamara B. Bone marrow micrometastases in patient with brain metastases from epithelial cell tumours. Q J Med. 2000;93:611-15.
  • Yazışma Adresi / Address for Correspondence: Dr. Berna Bozkurt Duman Cukurova University Faculty of Medicine Department of Medical Oncology Tel:+90322 338 60 60 Fax :+90322 338 70 10
  • E-mail: berboz@hotmail.com geliş tarihi/received :11.11.2013 kabul tarihi/accepted:09.12.2013
There are 31 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research
Authors

Mustafa Salih Akın This is me

Berna Bozkurt Duman This is me

Berksoy Sahin This is me

Publication Date July 22, 2014
Published in Issue Year 2014 Volume: 39 Issue: 2

Cite

MLA Akın, Mustafa Salih et al. “Bone Marrow Micrometastasis Detected by Flow Cytometry Is Associated Bone, Bone Marrow, Lung Macrometastasis in Breast Cancer”. Cukurova Medical Journal, vol. 39, no. 2, 2014, pp. 305-14, doi:10.17826/cutf.38648.