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European Radiology

, Volume 23, Issue 12, pp 3221–3227 | Cite as

BOLD-MRI of breast invasive ductal carcinoma: correlation of R2* value and the expression of HIF-1α

  • Min LiuEmail author
  • Xiaojuan Guo
  • Shuangkun Wang
  • Mulan Jin
  • Ying Wang
  • Jie Li
  • Jun Liu
Breast

Abstract

Objective

To explore the reliability and feasibility of blood oxygenation level-dependent-based functional magnetic resonance imaging (BOLD-fMRI) to depict hypoxia in breast invasive ductal carcinoma.

Methods

A total of 103 women with 104 invasive ductal carcinomas (IDCs) underwent breast BOLD-fMRI at 3.0 T. Histological specimens were analysed for tumour size, grade, axillary lymph nodes and expression of oestrogen receptors, progesterone receptors, human epidermal growth factor receptor 2, p53, Ki-67 and hypoxia inducible factor 1α (HIF-1α). The distribution and reliability of R2* were analysed. Correlations of the R2* value with the prognostic factors and HIF-1α were respectively analysed.

Results

The R2* map of IDC demonstrated a relatively heterogeneous signal. The mean R2* value was (53.4 ± 18.2) Hz. The Shapiro–Wilk test (W = 0.971, P = 0.020) suggested that the sample did not follow a normal distribution. The inter-rater and intrarater correlation coefficient was 0.967 and 0.959, respectively. The R2* values of IDCs were significantly lower in patients without axillary lymph nodes metastasis. The R2* value had a weak correlation with Ki67 expression (r = 0.208, P = 0.038). The mean R2* value correlated moderately with the level of HIF-1α (r = 0.516, P = 0.000).

Conclusion

BOLD-fMRI is a simple and non-invasive technique that yields hypoxia information on breast invasive ductal carcinomas.

Key Points

• Blood oxygenation level-dependent-based MRI can be used to assess tumour hypoxia.

• BOLD-fMRI shows characteristic features of breast invasive ductal carcinoma.

• R2* values of BOLD-fMRI correlate with hypoxia inducible factor 1α.

Keywords

Breast invasive ductal carcinoma Hypoxia Blood oxygen level-dependent effect Magnetic resonance imaging Hypoxia inducible factor 1α 

Notes

Acknowledgements

This research was supported by the Chinese National Scientific Research Foundation (30900364)

References

  1. 1.
    Stone HB, Brown JM, Phillips TL, Sutherland RM (1993) Oxygen in human tumors: correlations between methods of measurement and response to therapy. Summary of a workshop held November 19–20, 1992, at the National Cancer Institute, Bethesda, Maryland. Radiat Res 136:422–434PubMedCrossRefGoogle Scholar
  2. 2.
    Bussink J, Kaanders JH, van der Kogel AJ (2003) Tumor hypoxia at the microregional level: clinical relevance and predictive value of exogenous and endogenous hypoxic cell markers. Radiother Oncol 67:3–15PubMedCrossRefGoogle Scholar
  3. 3.
    Øvrebø KM, Hompland T, Mathiesen B, Rofstad EK (2012) Assessment of hypoxia and radiation response in intramuscular experimental tumors by dynamic contrast-enhanced magnetic resonance imaging. Radiother Oncol 102:429–435PubMedCrossRefGoogle Scholar
  4. 4.
    Gulliksrud K, Hompland T, Galappathi K, Rofstad EK (2011) Assessment of tumor hypoxia and interstitial fluid pressure by gadomelitol-based dynamic contrast-enhanced magnetic resonance imaging. Radiother Oncol 101:217–222PubMedCrossRefGoogle Scholar
  5. 5.
    Cooper RA, Carrington BM, Loncaster JA et al (2000) Tumour oxygenation levels correlate with dynamic contrast-enhanced magnetic resonance imaging parameters in carcinoma of the cervix. Radiother Oncol 57:53–59PubMedCrossRefGoogle Scholar
  6. 6.
    González Hernando C, Esteban L, Cañas T, Van den Brule E, Pastrana M (2010) The role of magnetic resonance imaging in oncology. Clin Transl Oncol 12:606–613PubMedCrossRefGoogle Scholar
  7. 7.
    Chopra S, Foltz WD, Milosevic MF et al (2009) Comparing oxygen-sensitive MRI (BOLD R2*) with oxygen electrode measurements: a pilot study in men with prostate cancer. Int J Radiat Biol 85:805–813PubMedCrossRefGoogle Scholar
  8. 8.
    McPhail LD, Robinson SP (2010) Intrinsic susceptibility MR imaging of chemically induced rat mammary tumors: relationship to histologic assessment of hypoxia and fibrosis. Radiology 254:110–118PubMedCrossRefGoogle Scholar
  9. 9.
    Li SP, Taylor NJ, Makris A et al (2010) Primary human breast adenocarcinoma: imaging and histologic correlates of intrinsic susceptibility-weighted MR imaging before and during chemotherapy. Radiology 257:643–652PubMedCrossRefGoogle Scholar
  10. 10.
    Zhong H, De Marzo AM, Laughner E et al (1999) Overexpression of hypoxia-inducible factor-1 alpha in common human cancers and their metastases. Cancer Res 59:5830–5835PubMedGoogle Scholar
  11. 11.
    Padhani AR, Krohn KA, Lewis JS, Alber M (2007) Imaging oxygenation of human tumours. Eur Radiol 17:861–872PubMedCrossRefGoogle Scholar
  12. 12.
    Vaupel P, Schlenger K, Knoop C, Hockel M (1991) Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements. Cancer Res 51:3316–3322PubMedGoogle Scholar
  13. 13.
    Hockel M, Schlenger K, Hockel S, Vaupel P (1991) Association between tumor hypoxia and malignant progression: the clinical evidence in cancer of the uterine cervix. In: Vaupel P, Kelleher DK (eds) Tumour hypoxia. Wissenschaftliche Verlagsgesellschaft, Stuttgart, pp 65–74Google Scholar
  14. 14.
    Padhani AR, Ah-See MLW, Taylor NJ et al. (2005) An investigation of histological and DC-MRI correlates of intrinsic susceptibility contrast relaxivity (R2*) in human breast cancer. In: Proceedings of the Thirteenth Meeting of the International Society for Magnetic Resonance in Medicine. International Society for Magnetic Resonance in Medicine, Berkeley, p 1846Google Scholar
  15. 15.
    Jatoi I, Hilsenbeck SG, Clark GM, Osborne CK (1999) Significance of axillary lymph node metastasis in primary breast cancer. J Clin Oncol 17:2334–2340PubMedGoogle Scholar
  16. 16.
    Mussurakis S, Buckley DL, Horsman A (1997) Prediction of axillary lymph node status in invasive breast cancer with dynamic contrast-enhanced MR imaging. Radiology 203:317–321PubMedGoogle Scholar
  17. 17.
    Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO (2007) Prognostic markers in triple-negative breast cancer. Cancer 109:25–32PubMedCrossRefGoogle Scholar
  18. 18.
    Kumar R, Yarmand-Bagheri R (2008) The role of C-ERBB-2 in angiogenesis. Semin Oncol 28:27–32CrossRefGoogle Scholar
  19. 19.
    Viale G, Regan MM, Mastropasqua MG et al (2008) International Breast Cancer Study Group. Predictive value of tumor Ki-67 expression in two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Natl Cancer Inst 100:207–212PubMedCrossRefGoogle Scholar
  20. 20.
    Xiang L, Liu ZH, Huan Q et al (2012) Hypoxia-inducible factor-2a is associated with ABCG2 expression, histology-grade and Ki67expression in breast invasive ductal carcinoma. Diagn Pathol 27:32CrossRefGoogle Scholar
  21. 21.
    Stephen RM, Pagel MD, Brown K, Baker AF, Meuillet EJ, Gillies RJ (2012) Monitoring the development of xenograft triple-negative breast cancer models using diffusion-weighted magnetic resonance imaging. Exp Biol Med (Maywood) 237:1273–1280CrossRefGoogle Scholar
  22. 22.
    Hoskin PJ, Carnell DM, Taylor NJ et al (2007) Hypoxia in prostate cancer: correlation of BOLD-MRI with pimonidazole immunohistochemistry-initial observations. Int J Radiat Oncol Biol Phys 68:1065–1071PubMedCrossRefGoogle Scholar
  23. 23.
    Alonzi R, Padhani AR, Maxwell RJ et al (2009) Carbogen breathing increases prostate cancer oxygenation: a translational MRI study in murine xenografts and humans. Br J Cancer 100:644–648PubMedCrossRefGoogle Scholar
  24. 24.
    Vaupel P, Harrison L (2004) Tumor hypoxia: causative factors, compensatory mechanisms, and cellular response. Oncologist 9:4–9PubMedCrossRefGoogle Scholar
  25. 25.
    Rodrigues LM, Howe FA, Griffiths JR, Robinson SP (2004) Tumor R2* is a prognostic indicator of acute radiotherapeutic response in rodent tumors. J Magn Reson Imaging 19:482–488PubMedCrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2013

Authors and Affiliations

  • Min Liu
    • 1
    Email author
  • Xiaojuan Guo
    • 1
  • Shuangkun Wang
    • 1
  • Mulan Jin
    • 2
  • Ying Wang
    • 2
  • Jie Li
    • 3
  • Jun Liu
    • 3
  1. 1.Department of Radiology, Beijing Chao Yang HospitalCapital Medical UniversityBeijingChina
  2. 2.Department of Pathology, Beijing Chaoyang HospitalCapital Medical University BeijingBeijingPeople’s Republic of China
  3. 3.Department of Breast Surgery, Beijing Chaoyang HospitalCapital Medical University BeijingBeijingPeople’s Republic of China

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