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Small breast epithelial mucin (SBEM) has the potential to be a marker for predicting hematogenous micrometastasis and response to neoadjuvant chemotherapy in breast cancer

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Abstract

To investigate the potential role of small breast epithelial mucin (SBEM) as a marker for detecting hematogenous micrometastasis in breast cancer and explore its clinical significance in neoadjuvant chemotherapy. SBEM protein expression in 82 tissue specimens of primary breast cancer was detected using immunohistochemistry (IHC), and SBEM expression in peripheral blood (PB) samples of 109 primary breast cancer patients (94 cases at stage I–III, 15 cases at stage IV) was detected by flow cytometry (FCM) and reverse transcription polymerase chain reaction (RT-PCR). Moreover, SBEM mRNA expression was monitored by quantification real-time PCR (QPCR) before and after 3 cycles’ neoadjuvant chemotherapy. SBEM expression correlated with tumor node metastasis (TNM) staging and lymph node metastasis at both mRNA and protein levels. SBEM expression in PB of breast cancer patients was markedly higher than that of healthy donors and other cancer patients. SBEM was found expressed in PB of 50 cases among 94 cases at stage I–III and expressed in PB of 11 cases among 15 cases at stage IV. After 3 cycles’ neoadjuvant chemotherapy, SBEM expression levels were significantly down-regulated in up to 58% breast cancer patients. SBEM has the potential to be a specific marker for predicting hematogenous micrometastasis and response to neoadjuvant chemotherapy in breast cancer.

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Abbreviations

SBEM:

Small breast epithelial mucin

IHC:

Immunohistochemistry

PB:

Peripheral blood

FCM:

Flow cytometry

RT–PCR:

Reverse transcription polymerase chain reaction

QPCR:

Quantification real-time PCR

TNM:

Tumor node metastasis

PBS:

Phosphate buffered saline

FITC:

Fluorescein isothiocyanate

GAPDH:

Gluceraldehyde 3-phosphate dehydrogenase

LNM:

Lymph node metastasis

HE:

Hematoxylin eosin

TMA:

Tissue microarray

References

  1. Anonymous (1991) Treatment of early-stage breast cancer: NIH consensus conference. J Am Med Assoc 265:391–395

    Google Scholar 

  2. Clark JW, Snell L, Shiu BPC et al (1999) The potential role for prolactin-inducible protein (PIP) as a marker of human breast cancer micrometastasis. British J Cancer 81:1002–1008

    Article  CAS  Google Scholar 

  3. Silva AL, Diamond J, Silva MR et al (2001) Cytokeratin 20 is not a reliable molecular marker for occult breast cancer cell detection in haematological tissues. Breast Cancer Res Treat 66:59–66

    Article  CAS  PubMed  Google Scholar 

  4. Ring A, Smith IE, Dowsett M (2004) Circulating tumour cells in breast cancer. Lancet Oncol 5:79–88

    Article  PubMed  Google Scholar 

  5. Felton T, Harris GC, Pinder SE et al (2004) Identification of carcinoma cells in peripheral blood samples of patients with advanced breast carcinoma using RT-PCR amplification of CK7 and MUC1. Breast 1:35–41

    Article  Google Scholar 

  6. Xenidis N, Perraki M, Kafousi M et al (2006) Predictive and prognostic value of peripheral blood cytokeratin-19 mRNA-positive cells detected by real-time polymerase chain reaction in node negative breast cancer patients. J Clin Oncol 24:3756–3762

    Article  CAS  PubMed  Google Scholar 

  7. Zieglschmid V, Hollmann C, Bo¨cher O (2005) Detection of disseminated tumor cells in peripheral blood. Crit Rev Clin Lab Sci 42:155–196

    Article  CAS  PubMed  Google Scholar 

  8. Ntoulia M, Stathopoulou A, Ignatiadis M et al (2006) Detection of Mammaglobin A-mRNA-positive circulating tumor cells in peripheral blood of patients with operable breast cancer with nested RT-PCR. Clin Biochem 39:879–887

    Article  CAS  PubMed  Google Scholar 

  9. Miksicek RJ, Myal Y, Watson PH et al (2002) Identification of a novel breast- and salivary gland-specific, mucin-like gene strongly expressed in normal and tumour human mammary epithelium. Cancer Res 62:2736–2740

    CAS  PubMed  Google Scholar 

  10. Valladares-Ayerbes M, Iglesias-Díaz P, Díaz-Prado S et al (2009) Diagnostic accuracy of small breast epithelial mucin mRNA as a marker for bone marrow micrometastasis in breast cancer: a pilot study. J Cancer Res Clin Oncol 135:1185–1195

    Article  CAS  PubMed  Google Scholar 

  11. Ayerbes MV, Díaz-Prado S, Ayude D et al (2008) In silico and in vitro analysis of small breast epithelial mucin as a marker for bone marrow micrometastasis in breast cancer. Adv Exp Med Biol 617:331–339

    Article  PubMed  Google Scholar 

  12. Jennbacken K, Valbo C, Wang W et al (2005) Expression of Vascular Endothelial Growth Factor C (VEGF-C) and VEGF Receptor-3 in human prostate cancer are associated with regional lymph node metastasis. Prostate 65:110–116

    Article  CAS  PubMed  Google Scholar 

  13. Pan AP, Huang GY, Chen J et al (2009) Relationship between hepatitis B virus covalently closed circular DNA and HBx protein expression in hepatocellular carcinoma and its significance. World Chin J Digestol 17:712–715

    CAS  Google Scholar 

  14. Skliris GP, Hube′ F, Gheorghiu I et al (2008) Expression of small breast epithelial mucin (SBEM) protein in tissue microarrays (TMAs) of primary invasive breast cancers. Histopathology 52:355–369

    Article  CAS  PubMed  Google Scholar 

  15. Luppi M, Morselli M, Bandieri E et al (1996) Sensitive detection of circulating breast cancer cells by reverse-transcriptase polymerase chain reaction of maspin gene. Ann Oncol 7:619–624

    CAS  PubMed  Google Scholar 

  16. Molloy TJ, Bosma AJ, van’t Veer Laura J (2008) Towards an optimized platform for the detection, enrichment, and semi-quantitation circulating tumor cells. Breast Cancer Res Treat 112:297–307

    Article  CAS  PubMed  Google Scholar 

  17. Ginzinger DG (2002) Gene quantification using real-time quantitative PCR: An emerging technology hits the mainstream. Exp Hematol 30:503–512

    Article  CAS  PubMed  Google Scholar 

  18. Lacroix M (2006) Significance, detection and markers of disseminated breast cancer cells. Endocr Relat Cancer 13:1033–1067

    Article  CAS  PubMed  Google Scholar 

  19. Cristofanilli M, Hayes DF, Budd GT et al (2005) Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 23:1420–1430

    Article  PubMed  Google Scholar 

  20. Wülfing P, Borchard J, Bürger H et al (2006) HER2-positive circulating tumor cells indicate poor clinical outcome in stages I to III breast cancer patients. Clin Cancer Res 12:1715–1720

    Article  PubMed  Google Scholar 

  21. Hube F, Mutawe M, Leygue E et al (2004) Human small breast epithelial mucin: the promise of a new breast tumour biomarker. DNA Cell Biol 23:842–894

    CAS  PubMed  Google Scholar 

  22. Brown NM, Stenzel TT, Friedman PN et al (2006) Evaluation of expression based markers for the detection of breast cancer cells. Breast Cancer Res Treat 97:41–47

    Article  PubMed  Google Scholar 

  23. Gilbey AM, Burnett D, Coleman RE et al (2004) The detection of circulating breast cancer cells. J Clin Pathol 57:903–911

    Article  CAS  PubMed  Google Scholar 

  24. Leers MP, Schoffelen RH, Hoop JG et al (2002) Multiparameter flow cytometry as a tool for the detection of micrometastatic tumour cells in the sentinel lymph node procedure of patients with breast cancer. J Clin Pathol 55:359–366

    Article  CAS  PubMed  Google Scholar 

  25. Beriwal S, Schwartz GF, Komarnicky L et al (2006) Breast conserving therapy after neoadjuvant chemotherapy: long term results. Breast J 12:159–164

    Article  PubMed  Google Scholar 

  26. Amat S, Abrial C, Penault-Llorca F et al (2005) High prognostic significance of residual disease after neoadjuvant chemotherapy: a retrospective study in 710 patients with operable breast cancer. Breast Cancer Res Treat 94:255–263

    Article  CAS  PubMed  Google Scholar 

  27. Xie XD, Qu SX (2007) Neoadjuvant chemotherapy in breast cancer. Chin J Pract Inter Med 27:1904–1907

    CAS  Google Scholar 

  28. Schwartz GF, Meltzer AJ, Lucarelli EA et al (2005) Breast conservation after neoadjuvant chemotherapy for stage II carcinoma of the breast. J Am Coll Surg 201:327–334

    Article  PubMed  Google Scholar 

  29. Hennessy BT, Gonzalez-Angulo AM, Hortobagyi GN (2005) Individualization of neoadjuvant therapy for breast cancer according to molecular tumor characteristics. Nat Clin Pract Oncol 2:598–599

    Article  PubMed  Google Scholar 

  30. Wu M, Zhang JX, Pang LQ et al (2007) Clinical significance of SBEM mRNA assay in peripheral blood from patients with breast cancer. J Jiangsu Univ (Med Edition) 17:241–243

    CAS  Google Scholar 

  31. Yang HW, Liu JL, Cao J et al (2005) The Studies on SBEM-mRNA and CD44V6-mRNA in Peripheral Blood of Patients with Breast Cancer. Chin J Clin Oncol 32:382–385

    CAS  Google Scholar 

  32. Ke F, Wu JM, Yao JE et al (2007) Application of suspension array assay to detect marker genes expression of circulating tumor cells for early prediction of breast cancer metastasis. Zhonghua Yi Xue Za Zhi 87:2257–2261

    CAS  PubMed  Google Scholar 

  33. Ho-Pun-Cheung A, Bascoul-Mollevi C, Assenat E et al (2009) Reverse transcription-quantitative polymerase chain reaction: description of a RIN-based algorithm for accurate data normalization. BMC Mol Biol 10:31. doi:10.1186/1471-2199-10-31

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Yang Ming for expert technical assistance with immunohistochemistry. We thank Dr. Piao Ying, Dr. Ding Zhenyu and Dr. Li Bing for secretarial and organizational support in our experiments. We also thank prof. Liu Yongye for critical revision of the manuscript.

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Correspondence to Xiao-Dong Xie.

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Liu, ZZ., Xie, XD., Qu, SX. et al. Small breast epithelial mucin (SBEM) has the potential to be a marker for predicting hematogenous micrometastasis and response to neoadjuvant chemotherapy in breast cancer. Clin Exp Metastasis 27, 251–259 (2010). https://doi.org/10.1007/s10585-010-9323-2

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  • DOI: https://doi.org/10.1007/s10585-010-9323-2

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