Abstract

The native fluorescence spectra of human cancerous and normal breast tissues were investigated using the selected excitation wavelength of 340 nm to excite key building block molecules, such as reduced nicotinamide adenine dinucleotide (NADH), collagen, and flavin. The measured emission spectra were analyzed using a non-negative constraint method, namely multivariate curve resolution with alternating least-squares (MCR-ALS). The results indicate that the biochemical changes of tissue can be exposed by native fluorescence spectra analysis. The MCR-ALS-extracted components corresponding to the key fluorophores in breast tissue, such as collagen, NADH, and flavin, show differences of relative contents of fluorophores in cancerous and normal breast tissues. This research demonstrates that the native fluorescence spectroscopy measurements are effective for detecting changes of fluorophores composition in tissues due to the development of cancer. Native fluorescence spectroscopy analyzed by MCR-ALS may have the potential to be a new armamentarium.

© 2013 Optical Society of America

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References

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  13. Y. Pu, W. B. Wang, B. B. Das, and R. R. Alfano, “Time-resolved spectral wing emission kinetics and optical imaging of human cancerous and normal prostate tissues,” Opt. Commun. 282, 4308–4314 (2009).
    [CrossRef]
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    [CrossRef]
  20. Y. Pu, G. C. Tang, W. B. Wang, H. E. Savage, S. P. Schantz, and R. R. Alfano, “Native fluorescence spectroscopic evaluation of chemotherapeutic effects on malignant cells using nonnegative matrix factorization analysis,” Technol. Cancer Res. Treat. 10, 113–120 (2011).
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    [CrossRef]
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    [CrossRef]
  23. F. Urbach, “Potential effects of altered solar ultraviolet radiation on human skin cancer,” Photochem. Photobiol. 50, 507–513 (1989).
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2013 (1)

Y. Pu, W. B. Wang, Y. Yang, and R. R. Alfano, “Stokes shift spectroscopic analysis of multi-fluorophores for human cancer detection in breast and prostate tissues,” J. Biomed. Opt. 18, 017005 (2013).
[CrossRef]

2012 (2)

Y. Pu, W. B. Wang, Y. Yang, and R. R. Alfano, “Stokes shift spectroscopy highlights differences of cancerous and normal human tissues,” Opt. Lett. 37, 3360–3362(2012).
[CrossRef]

Y. Sun, Y. Pu, Y. Yang, and R. R. Alfano, “Biomarkers spectral subspace for cancer detection,” J. Biomed. Opt. 17, 107005 (2012).
[CrossRef]

2011 (1)

Y. Pu, G. C. Tang, W. B. Wang, H. E. Savage, S. P. Schantz, and R. R. Alfano, “Native fluorescence spectroscopic evaluation of chemotherapeutic effects on malignant cells using nonnegative matrix factorization analysis,” Technol. Cancer Res. Treat. 10, 113–120 (2011).

2010 (1)

Y. Pu, W. Wang, G. Tang, and R. R. Alfano, “Changes of collagen and nicotinamide adenine dinucleotide in human cancerous and normal breast tissues studied using fluorescence spectroscopy with selective excitation wavelength,” J. Biomed. Opt. 15, 047008 (2010).
[CrossRef]

2009 (1)

Y. Pu, W. B. Wang, B. B. Das, and R. R. Alfano, “Time-resolved spectral wing emission kinetics and optical imaging of human cancerous and normal prostate tissues,” Opt. Commun. 282, 4308–4314 (2009).
[CrossRef]

2008 (1)

A. Besaratinia, S. Kim, and G. P. Pfeifer, “Rapid repair of UVA-induced oxidized purines and persistence of UVB-induced dipyrimidine lesions determine the mutagenicity of sunlight in mouse cells,” FASEB J. 22, 2379–2392 (2008).
[CrossRef]

2005 (2)

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65, 8766–8773 (2005).
[CrossRef]

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer by using Raman spectroscopy,” Proc. Natl. Acad. Sci. USA 102, 12371–12376 (2005).
[CrossRef]

2000 (2)

J. F. Simpson, R. Gray, L. G. Dressler, C. D. Cobau, C. I. Falkson, K. W. Gilchrist, K. J. Pandya, D. L. Page, and N. J. Robert, “Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the eastern cooperative oncology group companion study, EST 4189,” J. Clin. Oncol. 18, 2059–2069 (2000).

D. L. Heintzelman, R. Lotan, and R. R. Richards-Kortum, “Characterization of the autofluorescence of polymorphonuclear leukocytes, mononuclear leukocytes and cervical epithelial cancer cells for improved spectroscopic discrimination of inflammation from dysplasia,” Photochem. Photobiol. 71, 327–332 (2000).
[CrossRef]

1999 (1)

G. Fenhalls, D. M. Dent, and M. I. Parker, “Breast tumour cell-induced down-regulation of type I collagen mRNA in fibroblasts,” Br. J. Cancer 81, 1142–1149 (1999).
[CrossRef]

1994 (1)

I. Balslev, C. K. Axelsson, K. Zedeler, B. B. Rasmussen, B. Carstensen, and H. T. Mouridsen, “The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG),” Breast Cancer Res. Treat. 32, 281–290 (1994).
[CrossRef]

1991 (1)

C. W. Elston and I. O. Ellis, “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, 403–410 (1991).
[CrossRef]

1989 (1)

F. Urbach, “Potential effects of altered solar ultraviolet radiation on human skin cancer,” Photochem. Photobiol. 50, 507–513 (1989).
[CrossRef]

1987 (1)

R. R. Alfano, G. C. Tang, A. Pradhan, W. Lam, D. S. J. Choy, and E. Opher, “Fluorescence spectra from cancerous and normal human breast and lung tissues,” IEEE J. Quantum Electron. QE-23, 1806 –1811 (1987).
[CrossRef]

1984 (2)

C. W. Elston, “The assessment of histological differentiation in breast cancer,” Aust. N. Z. J. Surg. 54, 11–15 (1984).
[CrossRef]

R. R. Alfano, D. Tata, J. Cordero, P. Tomashefsky, F. Longo, and M. Alfano, “Laser induced fluorescence spectroscopy from native cancerous and normal tissue,” IEEE J. Quantum Electron. 20, 1507–1511 (1984).
[CrossRef]

1965 (1)

B. Chance, J. R. Williamson, D. Famieson, and B. Schoener, “Properties and kinetics of reduced pyridine nucleotide fluorescence of the isolated and in vivo rat heart,” Biochem. Z. 341, 357–377 (1965).

1957 (1)

H. J. G. Bloom and W. W. Richardson, “Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years,” Br. J. Cancer 11, 359–377 (1957).
[CrossRef]

Alfano, M.

R. R. Alfano, D. Tata, J. Cordero, P. Tomashefsky, F. Longo, and M. Alfano, “Laser induced fluorescence spectroscopy from native cancerous and normal tissue,” IEEE J. Quantum Electron. 20, 1507–1511 (1984).
[CrossRef]

Alfano, R. R.

Y. Pu, W. B. Wang, Y. Yang, and R. R. Alfano, “Stokes shift spectroscopic analysis of multi-fluorophores for human cancer detection in breast and prostate tissues,” J. Biomed. Opt. 18, 017005 (2013).
[CrossRef]

Y. Pu, W. B. Wang, Y. Yang, and R. R. Alfano, “Stokes shift spectroscopy highlights differences of cancerous and normal human tissues,” Opt. Lett. 37, 3360–3362(2012).
[CrossRef]

Y. Sun, Y. Pu, Y. Yang, and R. R. Alfano, “Biomarkers spectral subspace for cancer detection,” J. Biomed. Opt. 17, 107005 (2012).
[CrossRef]

Y. Pu, G. C. Tang, W. B. Wang, H. E. Savage, S. P. Schantz, and R. R. Alfano, “Native fluorescence spectroscopic evaluation of chemotherapeutic effects on malignant cells using nonnegative matrix factorization analysis,” Technol. Cancer Res. Treat. 10, 113–120 (2011).

Y. Pu, W. Wang, G. Tang, and R. R. Alfano, “Changes of collagen and nicotinamide adenine dinucleotide in human cancerous and normal breast tissues studied using fluorescence spectroscopy with selective excitation wavelength,” J. Biomed. Opt. 15, 047008 (2010).
[CrossRef]

Y. Pu, W. B. Wang, B. B. Das, and R. R. Alfano, “Time-resolved spectral wing emission kinetics and optical imaging of human cancerous and normal prostate tissues,” Opt. Commun. 282, 4308–4314 (2009).
[CrossRef]

R. R. Alfano, G. C. Tang, A. Pradhan, W. Lam, D. S. J. Choy, and E. Opher, “Fluorescence spectra from cancerous and normal human breast and lung tissues,” IEEE J. Quantum Electron. QE-23, 1806 –1811 (1987).
[CrossRef]

R. R. Alfano, D. Tata, J. Cordero, P. Tomashefsky, F. Longo, and M. Alfano, “Laser induced fluorescence spectroscopy from native cancerous and normal tissue,” IEEE J. Quantum Electron. 20, 1507–1511 (1984).
[CrossRef]

Axelsson, C. K.

I. Balslev, C. K. Axelsson, K. Zedeler, B. B. Rasmussen, B. Carstensen, and H. T. Mouridsen, “The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG),” Breast Cancer Res. Treat. 32, 281–290 (1994).
[CrossRef]

Balslev, I.

I. Balslev, C. K. Axelsson, K. Zedeler, B. B. Rasmussen, B. Carstensen, and H. T. Mouridsen, “The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG),” Breast Cancer Res. Treat. 32, 281–290 (1994).
[CrossRef]

Besaratinia, A.

A. Besaratinia, S. Kim, and G. P. Pfeifer, “Rapid repair of UVA-induced oxidized purines and persistence of UVB-induced dipyrimidine lesions determine the mutagenicity of sunlight in mouse cells,” FASEB J. 22, 2379–2392 (2008).
[CrossRef]

Bird, D. K.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65, 8766–8773 (2005).
[CrossRef]

Bloom, H. J. G.

H. J. G. Bloom and W. W. Richardson, “Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years,” Br. J. Cancer 11, 359–377 (1957).
[CrossRef]

Carstensen, B.

I. Balslev, C. K. Axelsson, K. Zedeler, B. B. Rasmussen, B. Carstensen, and H. T. Mouridsen, “The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG),” Breast Cancer Res. Treat. 32, 281–290 (1994).
[CrossRef]

Chance, B.

B. Chance, J. R. Williamson, D. Famieson, and B. Schoener, “Properties and kinetics of reduced pyridine nucleotide fluorescence of the isolated and in vivo rat heart,” Biochem. Z. 341, 357–377 (1965).

Choy, D. S. J.

R. R. Alfano, G. C. Tang, A. Pradhan, W. Lam, D. S. J. Choy, and E. Opher, “Fluorescence spectra from cancerous and normal human breast and lung tissues,” IEEE J. Quantum Electron. QE-23, 1806 –1811 (1987).
[CrossRef]

Cobau, C. D.

J. F. Simpson, R. Gray, L. G. Dressler, C. D. Cobau, C. I. Falkson, K. W. Gilchrist, K. J. Pandya, D. L. Page, and N. J. Robert, “Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the eastern cooperative oncology group companion study, EST 4189,” J. Clin. Oncol. 18, 2059–2069 (2000).

Cordero, J.

R. R. Alfano, D. Tata, J. Cordero, P. Tomashefsky, F. Longo, and M. Alfano, “Laser induced fluorescence spectroscopy from native cancerous and normal tissue,” IEEE J. Quantum Electron. 20, 1507–1511 (1984).
[CrossRef]

Crowe, J.

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer by using Raman spectroscopy,” Proc. Natl. Acad. Sci. USA 102, 12371–12376 (2005).
[CrossRef]

Das, B. B.

Y. Pu, W. B. Wang, B. B. Das, and R. R. Alfano, “Time-resolved spectral wing emission kinetics and optical imaging of human cancerous and normal prostate tissues,” Opt. Commun. 282, 4308–4314 (2009).
[CrossRef]

Dasari, R. R.

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer by using Raman spectroscopy,” Proc. Natl. Acad. Sci. USA 102, 12371–12376 (2005).
[CrossRef]

de Juan, A.

R. Tauler, M. Maeder, and A. de Juan, “Multi-set data analysis: extended multivariate curve resolution,” Comprehensive Chemometrics (Elsevier, 2009), pp. 473–506.

Dent, D. M.

G. Fenhalls, D. M. Dent, and M. I. Parker, “Breast tumour cell-induced down-regulation of type I collagen mRNA in fibroblasts,” Br. J. Cancer 81, 1142–1149 (1999).
[CrossRef]

Dressler, L. G.

J. F. Simpson, R. Gray, L. G. Dressler, C. D. Cobau, C. I. Falkson, K. W. Gilchrist, K. J. Pandya, D. L. Page, and N. J. Robert, “Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the eastern cooperative oncology group companion study, EST 4189,” J. Clin. Oncol. 18, 2059–2069 (2000).

Eliceiri, K. W.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65, 8766–8773 (2005).
[CrossRef]

Ellis, I. O.

C. W. Elston and I. O. Ellis, “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, 403–410 (1991).
[CrossRef]

Elston, C. W.

C. W. Elston and I. O. Ellis, “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, 403–410 (1991).
[CrossRef]

C. W. Elston, “The assessment of histological differentiation in breast cancer,” Aust. N. Z. J. Surg. 54, 11–15 (1984).
[CrossRef]

Falkson, C. I.

J. F. Simpson, R. Gray, L. G. Dressler, C. D. Cobau, C. I. Falkson, K. W. Gilchrist, K. J. Pandya, D. L. Page, and N. J. Robert, “Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the eastern cooperative oncology group companion study, EST 4189,” J. Clin. Oncol. 18, 2059–2069 (2000).

Famieson, D.

B. Chance, J. R. Williamson, D. Famieson, and B. Schoener, “Properties and kinetics of reduced pyridine nucleotide fluorescence of the isolated and in vivo rat heart,” Biochem. Z. 341, 357–377 (1965).

Feld, M. S.

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer by using Raman spectroscopy,” Proc. Natl. Acad. Sci. USA 102, 12371–12376 (2005).
[CrossRef]

Fenhalls, G.

G. Fenhalls, D. M. Dent, and M. I. Parker, “Breast tumour cell-induced down-regulation of type I collagen mRNA in fibroblasts,” Br. J. Cancer 81, 1142–1149 (1999).
[CrossRef]

Fitzmaurice, M.

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer by using Raman spectroscopy,” Proc. Natl. Acad. Sci. USA 102, 12371–12376 (2005).
[CrossRef]

Gilchrist, K. W.

J. F. Simpson, R. Gray, L. G. Dressler, C. D. Cobau, C. I. Falkson, K. W. Gilchrist, K. J. Pandya, D. L. Page, and N. J. Robert, “Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the eastern cooperative oncology group companion study, EST 4189,” J. Clin. Oncol. 18, 2059–2069 (2000).

Gray, R.

J. F. Simpson, R. Gray, L. G. Dressler, C. D. Cobau, C. I. Falkson, K. W. Gilchrist, K. J. Pandya, D. L. Page, and N. J. Robert, “Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the eastern cooperative oncology group companion study, EST 4189,” J. Clin. Oncol. 18, 2059–2069 (2000).

Haka, A. S.

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer by using Raman spectroscopy,” Proc. Natl. Acad. Sci. USA 102, 12371–12376 (2005).
[CrossRef]

Heintzelman, D. L.

D. L. Heintzelman, R. Lotan, and R. R. Richards-Kortum, “Characterization of the autofluorescence of polymorphonuclear leukocytes, mononuclear leukocytes and cervical epithelial cancer cells for improved spectroscopic discrimination of inflammation from dysplasia,” Photochem. Photobiol. 71, 327–332 (2000).
[CrossRef]

Keely, P. J.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65, 8766–8773 (2005).
[CrossRef]

Kim, S.

A. Besaratinia, S. Kim, and G. P. Pfeifer, “Rapid repair of UVA-induced oxidized purines and persistence of UVB-induced dipyrimidine lesions determine the mutagenicity of sunlight in mouse cells,” FASEB J. 22, 2379–2392 (2008).
[CrossRef]

Lam, W.

R. R. Alfano, G. C. Tang, A. Pradhan, W. Lam, D. S. J. Choy, and E. Opher, “Fluorescence spectra from cancerous and normal human breast and lung tissues,” IEEE J. Quantum Electron. QE-23, 1806 –1811 (1987).
[CrossRef]

Longo, F.

R. R. Alfano, D. Tata, J. Cordero, P. Tomashefsky, F. Longo, and M. Alfano, “Laser induced fluorescence spectroscopy from native cancerous and normal tissue,” IEEE J. Quantum Electron. 20, 1507–1511 (1984).
[CrossRef]

Lotan, R.

D. L. Heintzelman, R. Lotan, and R. R. Richards-Kortum, “Characterization of the autofluorescence of polymorphonuclear leukocytes, mononuclear leukocytes and cervical epithelial cancer cells for improved spectroscopic discrimination of inflammation from dysplasia,” Photochem. Photobiol. 71, 327–332 (2000).
[CrossRef]

Maeder, M.

R. Tauler, M. Maeder, and A. de Juan, “Multi-set data analysis: extended multivariate curve resolution,” Comprehensive Chemometrics (Elsevier, 2009), pp. 473–506.

Mouridsen, H. T.

I. Balslev, C. K. Axelsson, K. Zedeler, B. B. Rasmussen, B. Carstensen, and H. T. Mouridsen, “The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG),” Breast Cancer Res. Treat. 32, 281–290 (1994).
[CrossRef]

Opher, E.

R. R. Alfano, G. C. Tang, A. Pradhan, W. Lam, D. S. J. Choy, and E. Opher, “Fluorescence spectra from cancerous and normal human breast and lung tissues,” IEEE J. Quantum Electron. QE-23, 1806 –1811 (1987).
[CrossRef]

Page, D. L.

J. F. Simpson, R. Gray, L. G. Dressler, C. D. Cobau, C. I. Falkson, K. W. Gilchrist, K. J. Pandya, D. L. Page, and N. J. Robert, “Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the eastern cooperative oncology group companion study, EST 4189,” J. Clin. Oncol. 18, 2059–2069 (2000).

Pandya, K. J.

J. F. Simpson, R. Gray, L. G. Dressler, C. D. Cobau, C. I. Falkson, K. W. Gilchrist, K. J. Pandya, D. L. Page, and N. J. Robert, “Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the eastern cooperative oncology group companion study, EST 4189,” J. Clin. Oncol. 18, 2059–2069 (2000).

Parker, M. I.

G. Fenhalls, D. M. Dent, and M. I. Parker, “Breast tumour cell-induced down-regulation of type I collagen mRNA in fibroblasts,” Br. J. Cancer 81, 1142–1149 (1999).
[CrossRef]

Pfeifer, G. P.

A. Besaratinia, S. Kim, and G. P. Pfeifer, “Rapid repair of UVA-induced oxidized purines and persistence of UVB-induced dipyrimidine lesions determine the mutagenicity of sunlight in mouse cells,” FASEB J. 22, 2379–2392 (2008).
[CrossRef]

Pradhan, A.

R. R. Alfano, G. C. Tang, A. Pradhan, W. Lam, D. S. J. Choy, and E. Opher, “Fluorescence spectra from cancerous and normal human breast and lung tissues,” IEEE J. Quantum Electron. QE-23, 1806 –1811 (1987).
[CrossRef]

Pu, Y.

Y. Pu, W. B. Wang, Y. Yang, and R. R. Alfano, “Stokes shift spectroscopic analysis of multi-fluorophores for human cancer detection in breast and prostate tissues,” J. Biomed. Opt. 18, 017005 (2013).
[CrossRef]

Y. Pu, W. B. Wang, Y. Yang, and R. R. Alfano, “Stokes shift spectroscopy highlights differences of cancerous and normal human tissues,” Opt. Lett. 37, 3360–3362(2012).
[CrossRef]

Y. Sun, Y. Pu, Y. Yang, and R. R. Alfano, “Biomarkers spectral subspace for cancer detection,” J. Biomed. Opt. 17, 107005 (2012).
[CrossRef]

Y. Pu, G. C. Tang, W. B. Wang, H. E. Savage, S. P. Schantz, and R. R. Alfano, “Native fluorescence spectroscopic evaluation of chemotherapeutic effects on malignant cells using nonnegative matrix factorization analysis,” Technol. Cancer Res. Treat. 10, 113–120 (2011).

Y. Pu, W. Wang, G. Tang, and R. R. Alfano, “Changes of collagen and nicotinamide adenine dinucleotide in human cancerous and normal breast tissues studied using fluorescence spectroscopy with selective excitation wavelength,” J. Biomed. Opt. 15, 047008 (2010).
[CrossRef]

Y. Pu, W. B. Wang, B. B. Das, and R. R. Alfano, “Time-resolved spectral wing emission kinetics and optical imaging of human cancerous and normal prostate tissues,” Opt. Commun. 282, 4308–4314 (2009).
[CrossRef]

Ramanujam, N.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65, 8766–8773 (2005).
[CrossRef]

Rasmussen, B. B.

I. Balslev, C. K. Axelsson, K. Zedeler, B. B. Rasmussen, B. Carstensen, and H. T. Mouridsen, “The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG),” Breast Cancer Res. Treat. 32, 281–290 (1994).
[CrossRef]

Richards-Kortum, R. R.

D. L. Heintzelman, R. Lotan, and R. R. Richards-Kortum, “Characterization of the autofluorescence of polymorphonuclear leukocytes, mononuclear leukocytes and cervical epithelial cancer cells for improved spectroscopic discrimination of inflammation from dysplasia,” Photochem. Photobiol. 71, 327–332 (2000).
[CrossRef]

Richardson, W. W.

H. J. G. Bloom and W. W. Richardson, “Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years,” Br. J. Cancer 11, 359–377 (1957).
[CrossRef]

Robert, N. J.

J. F. Simpson, R. Gray, L. G. Dressler, C. D. Cobau, C. I. Falkson, K. W. Gilchrist, K. J. Pandya, D. L. Page, and N. J. Robert, “Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the eastern cooperative oncology group companion study, EST 4189,” J. Clin. Oncol. 18, 2059–2069 (2000).

Savage, H. E.

Y. Pu, G. C. Tang, W. B. Wang, H. E. Savage, S. P. Schantz, and R. R. Alfano, “Native fluorescence spectroscopic evaluation of chemotherapeutic effects on malignant cells using nonnegative matrix factorization analysis,” Technol. Cancer Res. Treat. 10, 113–120 (2011).

Scarff, R. W.

R. W. Scarff and H. Torloni, “Histological typing of breast tumors,” in International Histological Classification of Tumours (World Health Organization, 1968).

Schantz, S. P.

Y. Pu, G. C. Tang, W. B. Wang, H. E. Savage, S. P. Schantz, and R. R. Alfano, “Native fluorescence spectroscopic evaluation of chemotherapeutic effects on malignant cells using nonnegative matrix factorization analysis,” Technol. Cancer Res. Treat. 10, 113–120 (2011).

Schoener, B.

B. Chance, J. R. Williamson, D. Famieson, and B. Schoener, “Properties and kinetics of reduced pyridine nucleotide fluorescence of the isolated and in vivo rat heart,” Biochem. Z. 341, 357–377 (1965).

Shafer-Peltier, K. E.

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer by using Raman spectroscopy,” Proc. Natl. Acad. Sci. USA 102, 12371–12376 (2005).
[CrossRef]

Simpson, J. F.

J. F. Simpson, R. Gray, L. G. Dressler, C. D. Cobau, C. I. Falkson, K. W. Gilchrist, K. J. Pandya, D. L. Page, and N. J. Robert, “Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the eastern cooperative oncology group companion study, EST 4189,” J. Clin. Oncol. 18, 2059–2069 (2000).

Sun, Y.

Y. Sun, Y. Pu, Y. Yang, and R. R. Alfano, “Biomarkers spectral subspace for cancer detection,” J. Biomed. Opt. 17, 107005 (2012).
[CrossRef]

Tang, G.

Y. Pu, W. Wang, G. Tang, and R. R. Alfano, “Changes of collagen and nicotinamide adenine dinucleotide in human cancerous and normal breast tissues studied using fluorescence spectroscopy with selective excitation wavelength,” J. Biomed. Opt. 15, 047008 (2010).
[CrossRef]

Tang, G. C.

Y. Pu, G. C. Tang, W. B. Wang, H. E. Savage, S. P. Schantz, and R. R. Alfano, “Native fluorescence spectroscopic evaluation of chemotherapeutic effects on malignant cells using nonnegative matrix factorization analysis,” Technol. Cancer Res. Treat. 10, 113–120 (2011).

R. R. Alfano, G. C. Tang, A. Pradhan, W. Lam, D. S. J. Choy, and E. Opher, “Fluorescence spectra from cancerous and normal human breast and lung tissues,” IEEE J. Quantum Electron. QE-23, 1806 –1811 (1987).
[CrossRef]

Tata, D.

R. R. Alfano, D. Tata, J. Cordero, P. Tomashefsky, F. Longo, and M. Alfano, “Laser induced fluorescence spectroscopy from native cancerous and normal tissue,” IEEE J. Quantum Electron. 20, 1507–1511 (1984).
[CrossRef]

Tauler, R.

R. Tauler, M. Maeder, and A. de Juan, “Multi-set data analysis: extended multivariate curve resolution,” Comprehensive Chemometrics (Elsevier, 2009), pp. 473–506.

Tomashefsky, P.

R. R. Alfano, D. Tata, J. Cordero, P. Tomashefsky, F. Longo, and M. Alfano, “Laser induced fluorescence spectroscopy from native cancerous and normal tissue,” IEEE J. Quantum Electron. 20, 1507–1511 (1984).
[CrossRef]

Torloni, H.

R. W. Scarff and H. Torloni, “Histological typing of breast tumors,” in International Histological Classification of Tumours (World Health Organization, 1968).

Urbach, F.

F. Urbach, “Potential effects of altered solar ultraviolet radiation on human skin cancer,” Photochem. Photobiol. 50, 507–513 (1989).
[CrossRef]

Vaughan, E. M.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65, 8766–8773 (2005).
[CrossRef]

Vrotsos, K. M.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65, 8766–8773 (2005).
[CrossRef]

Wang, W.

Y. Pu, W. Wang, G. Tang, and R. R. Alfano, “Changes of collagen and nicotinamide adenine dinucleotide in human cancerous and normal breast tissues studied using fluorescence spectroscopy with selective excitation wavelength,” J. Biomed. Opt. 15, 047008 (2010).
[CrossRef]

Wang, W. B.

Y. Pu, W. B. Wang, Y. Yang, and R. R. Alfano, “Stokes shift spectroscopic analysis of multi-fluorophores for human cancer detection in breast and prostate tissues,” J. Biomed. Opt. 18, 017005 (2013).
[CrossRef]

Y. Pu, W. B. Wang, Y. Yang, and R. R. Alfano, “Stokes shift spectroscopy highlights differences of cancerous and normal human tissues,” Opt. Lett. 37, 3360–3362(2012).
[CrossRef]

Y. Pu, G. C. Tang, W. B. Wang, H. E. Savage, S. P. Schantz, and R. R. Alfano, “Native fluorescence spectroscopic evaluation of chemotherapeutic effects on malignant cells using nonnegative matrix factorization analysis,” Technol. Cancer Res. Treat. 10, 113–120 (2011).

Y. Pu, W. B. Wang, B. B. Das, and R. R. Alfano, “Time-resolved spectral wing emission kinetics and optical imaging of human cancerous and normal prostate tissues,” Opt. Commun. 282, 4308–4314 (2009).
[CrossRef]

White, J. G.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65, 8766–8773 (2005).
[CrossRef]

Williamson, J. R.

B. Chance, J. R. Williamson, D. Famieson, and B. Schoener, “Properties and kinetics of reduced pyridine nucleotide fluorescence of the isolated and in vivo rat heart,” Biochem. Z. 341, 357–377 (1965).

Yan, L.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65, 8766–8773 (2005).
[CrossRef]

Yang, Y.

Y. Pu, W. B. Wang, Y. Yang, and R. R. Alfano, “Stokes shift spectroscopic analysis of multi-fluorophores for human cancer detection in breast and prostate tissues,” J. Biomed. Opt. 18, 017005 (2013).
[CrossRef]

Y. Pu, W. B. Wang, Y. Yang, and R. R. Alfano, “Stokes shift spectroscopy highlights differences of cancerous and normal human tissues,” Opt. Lett. 37, 3360–3362(2012).
[CrossRef]

Y. Sun, Y. Pu, Y. Yang, and R. R. Alfano, “Biomarkers spectral subspace for cancer detection,” J. Biomed. Opt. 17, 107005 (2012).
[CrossRef]

Zedeler, K.

I. Balslev, C. K. Axelsson, K. Zedeler, B. B. Rasmussen, B. Carstensen, and H. T. Mouridsen, “The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG),” Breast Cancer Res. Treat. 32, 281–290 (1994).
[CrossRef]

Aust. N. Z. J. Surg. (1)

C. W. Elston, “The assessment of histological differentiation in breast cancer,” Aust. N. Z. J. Surg. 54, 11–15 (1984).
[CrossRef]

Biochem. Z. (1)

B. Chance, J. R. Williamson, D. Famieson, and B. Schoener, “Properties and kinetics of reduced pyridine nucleotide fluorescence of the isolated and in vivo rat heart,” Biochem. Z. 341, 357–377 (1965).

Br. J. Cancer (2)

G. Fenhalls, D. M. Dent, and M. I. Parker, “Breast tumour cell-induced down-regulation of type I collagen mRNA in fibroblasts,” Br. J. Cancer 81, 1142–1149 (1999).
[CrossRef]

H. J. G. Bloom and W. W. Richardson, “Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years,” Br. J. Cancer 11, 359–377 (1957).
[CrossRef]

Breast Cancer Res. Treat. (1)

I. Balslev, C. K. Axelsson, K. Zedeler, B. B. Rasmussen, B. Carstensen, and H. T. Mouridsen, “The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG),” Breast Cancer Res. Treat. 32, 281–290 (1994).
[CrossRef]

Cancer Res. (1)

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65, 8766–8773 (2005).
[CrossRef]

FASEB J. (1)

A. Besaratinia, S. Kim, and G. P. Pfeifer, “Rapid repair of UVA-induced oxidized purines and persistence of UVB-induced dipyrimidine lesions determine the mutagenicity of sunlight in mouse cells,” FASEB J. 22, 2379–2392 (2008).
[CrossRef]

Histopathology (1)

C. W. Elston and I. O. Ellis, “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, 403–410 (1991).
[CrossRef]

IEEE J. Quantum Electron. (2)

R. R. Alfano, D. Tata, J. Cordero, P. Tomashefsky, F. Longo, and M. Alfano, “Laser induced fluorescence spectroscopy from native cancerous and normal tissue,” IEEE J. Quantum Electron. 20, 1507–1511 (1984).
[CrossRef]

R. R. Alfano, G. C. Tang, A. Pradhan, W. Lam, D. S. J. Choy, and E. Opher, “Fluorescence spectra from cancerous and normal human breast and lung tissues,” IEEE J. Quantum Electron. QE-23, 1806 –1811 (1987).
[CrossRef]

J. Biomed. Opt. (3)

Y. Sun, Y. Pu, Y. Yang, and R. R. Alfano, “Biomarkers spectral subspace for cancer detection,” J. Biomed. Opt. 17, 107005 (2012).
[CrossRef]

Y. Pu, W. Wang, G. Tang, and R. R. Alfano, “Changes of collagen and nicotinamide adenine dinucleotide in human cancerous and normal breast tissues studied using fluorescence spectroscopy with selective excitation wavelength,” J. Biomed. Opt. 15, 047008 (2010).
[CrossRef]

Y. Pu, W. B. Wang, Y. Yang, and R. R. Alfano, “Stokes shift spectroscopic analysis of multi-fluorophores for human cancer detection in breast and prostate tissues,” J. Biomed. Opt. 18, 017005 (2013).
[CrossRef]

J. Clin. Oncol. (1)

J. F. Simpson, R. Gray, L. G. Dressler, C. D. Cobau, C. I. Falkson, K. W. Gilchrist, K. J. Pandya, D. L. Page, and N. J. Robert, “Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the eastern cooperative oncology group companion study, EST 4189,” J. Clin. Oncol. 18, 2059–2069 (2000).

Opt. Commun. (1)

Y. Pu, W. B. Wang, B. B. Das, and R. R. Alfano, “Time-resolved spectral wing emission kinetics and optical imaging of human cancerous and normal prostate tissues,” Opt. Commun. 282, 4308–4314 (2009).
[CrossRef]

Opt. Lett. (1)

Photochem. Photobiol. (2)

D. L. Heintzelman, R. Lotan, and R. R. Richards-Kortum, “Characterization of the autofluorescence of polymorphonuclear leukocytes, mononuclear leukocytes and cervical epithelial cancer cells for improved spectroscopic discrimination of inflammation from dysplasia,” Photochem. Photobiol. 71, 327–332 (2000).
[CrossRef]

F. Urbach, “Potential effects of altered solar ultraviolet radiation on human skin cancer,” Photochem. Photobiol. 50, 507–513 (1989).
[CrossRef]

Proc. Natl. Acad. Sci. USA (1)

A. S. Haka, K. E. Shafer-Peltier, M. Fitzmaurice, J. Crowe, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer by using Raman spectroscopy,” Proc. Natl. Acad. Sci. USA 102, 12371–12376 (2005).
[CrossRef]

Technol. Cancer Res. Treat. (1)

Y. Pu, G. C. Tang, W. B. Wang, H. E. Savage, S. P. Schantz, and R. R. Alfano, “Native fluorescence spectroscopic evaluation of chemotherapeutic effects on malignant cells using nonnegative matrix factorization analysis,” Technol. Cancer Res. Treat. 10, 113–120 (2011).

Other (3)

R. Tauler, M. Maeder, and A. de Juan, “Multi-set data analysis: extended multivariate curve resolution,” Comprehensive Chemometrics (Elsevier, 2009), pp. 473–506.

American Cancer Society, “Cancer facts & figures 2012,” Atlanta: American Cancer Society (2012).

R. W. Scarff and H. Torloni, “Histological typing of breast tumors,” in International Histological Classification of Tumours (World Health Organization, 1968).

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Figures (5)

Fig. 1.
Fig. 1.

Average fluorescence spectra of cancerous (solid) and normal (dash) breast tissues obtained with the selective excitation wavelength of 340 nm.

Fig. 2.
Fig. 2.

Comparison of spectra of three PCs (solid) extracted from the fluorescence spectra of breast tissue using the MCR-ALS method and the measured (dash) spectra of individual collagen (elastin), NADH, and flavin.

Fig. 3.
Fig. 3.

(a) Relative content of the first PC, collagen, versus that of the second PC, NADH. (b) Relative content of the second PC, NADH, versus that of the third PC, flavin, generated by analyzing emission spectra of the 22 pairs of cancerous and normal breast tissues obtained with the 340 nm excitation using the MCR-ALS method. The separating lines were calculated using the LDA method by treating the 22 pairs of data as training samples. The relative content extracted from 16 other pairs of data as testing samples for (c) collagen versus NADH, and (d) NADH versus flavin. They are used to evaluate performance and accuracy of the criteria separating lines generated by the LDA algorithm using the 22 training samples.

Fig. 4.
Fig. 4.

(a) Relative content of the first PC, collagen, versus that of the second PC, NADH. (b) Relative content of the second PC, NADH, versus that of the third PC, flavin, generated by analyzing emission spectra of the total 38 pairs of cancerous and normal breast tissues obtained with the 340 nm excitation using the MCR-ALS method. The separating lines were calculated using the LDA method. (c) ROC curve obtained using scatter plot of the first PC, collagen, versus the second PC, NADH. (d) ROC curve obtained using scatter plot of the second PC, NADH, versus the third PC, flavin, as the pairs of diagnostically significant fluorophores to evaluate performance of classifying breast tissues into two groups: cancer and normal.

Fig. 5.
Fig. 5.

Microscopic images of the (a) cancerous and (b) normal breast tissue samples. The magnificent factor for microscopic images is 40×. The cancer is diagnosed as DCIS grade 3 by a pathology medical doctor. The fluorescence spectra of (a) cancerous and (b) normal breast tissues were obtained with the excitation of 340 nm.

Tables (3)

Tables Icon

Table 1. Absorption and Emission Peaks of the Key Fluorophores of Interest

Tables Icon

Table 2. Sensitivity and Specificity of Classing Cancerous and Normal Breast Tissues Using Native Fluorescence Spectroscopy and the LDA Algorithm

Tables Icon

Table 3. Comparison of Criteria Separating Lines and AUC Using 22 and 38 data Pairs for Cancerous and Normal Breast Tissues

Metrics