Skip to main content

Advertisement

Log in

Analysis of Cancer Marker in Tissues with Hadamard Transform Fluorescence Spectral Microscopic Imaging

  • ORIGINAL PAPER
  • Published:
Journal of Fluorescence Aims and scope Submit manuscript

Abstract

Quantum dots (QDs) probes were used to tag and trace cancer biomarkers in cancer tissues based on the system of home-made Hadamard transform (HT) spectral microscopic imaging, which can be applied to provide high-resolution fluorescence spectrum and image of single cells and tissues. In situ fluorescence imaging for cancer marker proteins, such as estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), proliferating cell nuclear antigen (PCNA) and cytokeratin 20 (CK20) in tumor tissues, were realized by using the HT system to capture quantitative information for these proteins when tumor tissues were immunostained with QDs probes. A method to evaluate tumor malignancy of the specimens based on in situ analysis of distribution of marker proteins was proposed based on the comparative study of positive samples and negative controls. The investigation of ER contents of the cores in breast cancer tissue microarrays (TMAs) shows that the technique of QDs-immunohistochemistry (IHC)/HT spectral imaging is more sensitive than conventional IHC method. The results also demonstrate that the QDs-IHC/HT spectral imaging technique can be applied to visualize and quantitatively measure the subcellular molecules inside tumor tissues, and the coupling of HT spectral imaging to the probing of subcellular molecules with QDs has great potential in biology and medical diagnosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Jensen EV, Cheng GJ, Palmieri C, Saji S, Makela S, Van Noorden S, Wahlstrom T, Warner M, Coombes RC, Gustafsson JA (2001) Estrogen receptors and proliferation markers in primary and recurrent breast cancer. Proc Natl Acad Sci U S A 98:15197–15202

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Hudis CA (2007) Drug therapy: trastuzumab - mechanism of action and use in clinical practice. N Engl J Med 357:39–51

    Article  CAS  PubMed  Google Scholar 

  3. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A, Press MF (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244:707–712

    Article  CAS  PubMed  Google Scholar 

  4. Hayes DF, Thor AD, Dressler LG, Weaver D, Edgerton S, Cowan D, Broadwater G, Goldstein LJ, Martino S, Ingle JN, Henderson IC, Norton L, Winer EP, Hudis CA, Ellis MJ, Berry DA (2007) HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med 357:1496–1506

    Article  CAS  PubMed  Google Scholar 

  5. Payne SJ, Bowen RL, Jones JL, Wells CA (2008) Predictive markers in breast cancer—the present. Histopathology 52:82–90

    Article  CAS  PubMed  Google Scholar 

  6. Naryzhny SN (2008) Proliferating cell nuclear antigen: a proteomics view. Cell Mol Life Sci 65:3789–3808

    Article  CAS  PubMed  Google Scholar 

  7. Moldovan GL, Pfander B, Jentsch S (2007) PCNA, the maestro of the replication fork. Cell 129:665–679

    Article  CAS  PubMed  Google Scholar 

  8. Fonseca FLA, Ana AVLS, Bendit I, Arias V, Costa LJ, Pinhal AA, del Giglio A (2005) Systemic chemotherapy induces microsatellite instability in the peripheral blood mononuclear cells of breast cancer patients. Breast Cancer Res 7:28–32

    Article  Google Scholar 

  9. Hoeller D, Hecker C-M, Dikic I (2006) Ubiquitin and ubiquitin-like proteins in cancer pathogenesis. Nat Rev Cancer 6:776–788

    Article  CAS  PubMed  Google Scholar 

  10. Couvelard A, Cauvin J-M, Goldfain D, Rotenberg A, Robaszkiewicz M, Flejou J-F (2001) Cytokeratin immunoreactivity of intestinal metaplasia at normal oesophagogastric junction indicates its aetiology. Gut 49:761–766

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Braun S, Pantel K (1999) Micrometastatic bone marrow involvement detection and prognostic significance. Med Oncol 16:154–165

    Article  CAS  PubMed  Google Scholar 

  12. Chen C, Chen L, Zhang Z, Li Y (2008) Advances in the application of quantum dots in tumor markers investigation. Chinese-German J Clin Oncol 7:179–184

    Article  Google Scholar 

  13. Gill R, Zayats M, Willner I (2008) Semiconductor quantum dots for bioanalysis. Angew Chem Int Ed 47:7602–7625

    Article  CAS  Google Scholar 

  14. Chen C, Peng J, Xia H-S, Yang G-F, Qiong-Shui W, Chen L-D, Zeng L-B, Zhang Z-L, Pang D-W, Li Y (2009) Quantum dots-based immunofluorescence technology for the quantitative determination of Her2 expression in breast cancer. Biomaterials 30:2912–2918

    Article  CAS  PubMed  Google Scholar 

  15. Xu H, Peng J, Tang HW, Li Y, Wu QS, Zhang ZL, Zhou G, Chen C, Li Y (2009) Hadamard transform spectral microscopy for single cell imaging using organic and quantum dot fluorescent probes. Analyst 134:504–511

    Article  CAS  PubMed  Google Scholar 

  16. Harwit M, Sloane NJA (1979) Hadamard transform optics. Academic, New York

    Google Scholar 

  17. Treado PJ, Morris MD (1988) Hadamard Transform Raman imaging. Appl Spectrosc 42:897–901

    Article  CAS  Google Scholar 

  18. Treado PJ, Morris MD (1989) A Hadamard Transform Raman microprobe. Appl Spectrosc 43:190–193

    Article  CAS  Google Scholar 

  19. Fotiou FK, Morris MD (1986) Hadamard Transform photothermal deflection imaging. Appl Spectrosc 40:704–706

    Article  CAS  Google Scholar 

  20. Treado PJ, Morris MD (1989) A thousand points of light: the Hadamard transform in chemical analysis and instrumentation. Anal Chem 61:723A–734A

    CAS  PubMed  Google Scholar 

  21. Tang HW, Luo MN, Li T, Pan L (2006) Quantitative DNA imaging in breast tumor cells by a Hadamard Transform fluorescence imaging microscope. Anal Sci 22:701–707

    Article  CAS  PubMed  Google Scholar 

  22. Xu H, Chen C, Peng J, Tang H-W, Liu C-M, He Y, Chen Z-Z, Li Y, Zhang Z-L, Pang D-W (2010) Evaluation of the bioconjugation efficiency of different quantum dots as probes for immunostaining tumor-marker proteins. Appl Spectrosc 64:847–852

    Article  CAS  PubMed  Google Scholar 

  23. He Y, Xu H, Chen C, Peng J, Tang H, Zhang Z, Li Y, Pang D (2011) In situ spectral imaging of marker proteins in gastric cancer with near-infrared and visible quantum dots probes. Talanta 85:136–141

    Article  CAS  PubMed  Google Scholar 

  24. Chen C, Peng J, Xia H, Wu Q, Zeng L, Xu H, Tang HW, Zhang ZL, Zhu X, Pang DW, Li Y (2010) Quantum-dot-based immunofluorescent imaging of HER2 and ER provides new insights into breast cancer heterogeneity. Nanotechnology 21:095101

    Article  PubMed  Google Scholar 

  25. Voduc D, Kenney C, Nielsen TO (2008) Tissue microarrays in clinical oncology. Semin Radiat Oncol 18:89–97

    Article  PubMed Central  PubMed  Google Scholar 

  26. Camp RL, Neumeister V, Rimm DL (2008) A decade of tissue microarrays: progress in the discovery and validation of cancer biomarkers. J Clin Oncol 26:5630–5637

    Article  PubMed  Google Scholar 

  27. Xing Y, Chaudry Q, Shen C, Kong KY, Zhau HE, Chung LW, Petros JA, O’Regan RM, Yezhelyev MV, Simons JW, Wang MD, Nie SM (2007) Bioconjugated quantum dots for multiplexed and quantitative immunohistochemistry. Nat Protoc 2:1152–1165

    Article  CAS  PubMed  Google Scholar 

  28. Mansfield JR, Gossage KW, Hoyt CC, Levenson RM (2005) Autofluorescence removal, multiplexing, and automated analysis methods for in-vivo fluorescence imaging. J Biomed Opt 10:041207

    Article  Google Scholar 

  29. van der Loos CM (2010) Chromogens in multiple immunohistochemical staining used for visual assessment and spectral imaging: the colorful future. J Histotechnol 33:31–40

    Article  Google Scholar 

Download references

Acknowledgments

We gratefully acknowledge the support of the National Basic Research Program of China (973 Program, nos. 2011CB933600 and 2006CB933100), the Science Fund for Creative Research Groups of NSFC (nos. 20621502 and 20921062), the National Natural Science Foundation of China (21275110, 21005056), and the Fundamental Research Funds for the Central Universities (20100141110015).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Hao Xu or Hong-Wu Tang.

Additional information

This work was supported by the National Basic Research Program of China (973 Program, nos. 2011CB933600 and 2006CB933100), the Science Fund for Creative Research Groups of NSFC (nos. 20621502 and 20921062), the National Natural Science Foundation of China (21275110, 21005056), and the Fundamental Research Funds for the Central Universities (20100141110015).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, H., Chen, C., He, Y. et al. Analysis of Cancer Marker in Tissues with Hadamard Transform Fluorescence Spectral Microscopic Imaging. J Fluoresc 25, 397–402 (2015). https://doi.org/10.1007/s10895-015-1525-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10895-015-1525-1

Keywords

Navigation