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Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 4, Iss. 11 — Nov. 1, 2013
  • pp: 2696–2709

Quantitative physiology and immunohistochemistry of oral lesions

Li-Tzu Lee, Po-Hsiung Chen, Chiou-Tuz Chang, John Wang, Yong-Kie Wong, and Hsing-Wen Wang  »View Author Affiliations

Biomedical Optics Express, Vol. 4, Issue 11, pp. 2696-2709 (2013)

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Angiogenesis and hypoxia are reported to correlate with tumor aggressiveness. In this study, we investigated the potential of optically measured total hemoglobin concentration (THC) and blood oxygen saturation (StO2) as a quantitative measure of angiogenesis and hypoxia in oral lesions with an immunohistochemical comparison. 12 normal subjects and 40 oral patients (22 oral squamous cell carcinoma (SCC), 18 benign/premalignant lesions including 11 verrucous hyperplasia (VH) and 7 hyperkeratosis/parakeratosis (HK)) were studied. The results showed that the THC measurement was consistent with vascular endothelial growth factor (VEGF) and microvessel staining in the stromal area, but StO2 was not associated with HIF-1α. We observed inflammation induced neovascular formation in the stromal area of VH and HK that were likely attributed to higher-than-control THC and StO2 and resulted in no difference in optical measurements between all lesions. However, we found that in majority of SCC, the ratio of THC and StO2 levels between lesions and the surrounding tissues provide potential distinguishing characteristics from VH, which are not visually differentiable from SCC, with a sensitivity, specificity, and accuracy of 91%, 68%, and 76%, respectively.

© 2013 Optical Society of America

OCIS Codes
(170.1610) Medical optics and biotechnology : Clinical applications
(170.1850) Medical optics and biotechnology : Dentistry
(170.5280) Medical optics and biotechnology : Photon migration
(300.0300) Spectroscopy : Spectroscopy

ToC Category:
Optics in Cancer Research

Original Manuscript: August 12, 2013
Revised Manuscript: October 17, 2013
Manuscript Accepted: October 22, 2013
Published: October 29, 2013

Li-Tzu Lee, Po-Hsiung Chen, Chiou-Tuz Chang, John Wang, Yong-Kie Wong, and Hsing-Wen Wang, "Quantitative physiology and immunohistochemistry of oral lesions," Biomed. Opt. Express 4, 2696-2709 (2013)

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  1. GLOBOCAN (IARC, 2008) Section of Cancer Information. http://globocan.iarc.fr/factsheets/populations/factsheet.asp?uno=900
  2. B. W. Neville, T. A. Day, “Oral cancer and precancerous lesions,” CA Cancer J. Clin. 52(4), 195–215 (2002). [CrossRef] [PubMed]
  3. J. J. Sciubba, “Oral cancer. The importance of early diagnosis and treatment,” Am. J. Clin. Dermatol. 2(4), 239–251 (2001). [CrossRef] [PubMed]
  4. W. H. Binnie and K. V. Rankin, Oral cancer: clinical and pathologic correlations (CRC Press, Boca Raton, 1998).
  5. M. W. Lingen, J. R. Kalmar, T. Karrison, P. M. Speight, “Critical evaluation of diagnostic aids for the detection of oral cancer,” Oral Oncol. 44(1), 10–22 (2008). [CrossRef] [PubMed]
  6. A. Gillenwater, V. Papadimitrakopoulou, R. Richards-Kortum, “Oral premalignancy: new methods of detection and treatment,” Curr. Oncol. Rep. 8(2), 146–154 (2006). [CrossRef] [PubMed]
  7. A. Amelink, O. P. Kaspers, H. J. Sterenborg, J. E. van der Wal, J. L. Roodenburg, M. J. Witjes, “Non-invasive measurement of the morphology and physiology of oral mucosa by use of optical spectroscopy,” Oral Oncol. 44(1), 65–71 (2008). [CrossRef] [PubMed]
  8. A. Amelink, H. J. Sterenborg, J. L. Roodenburg, M. J. Witjes, “Non-invasive measurement of the microvascular properties of non-dysplastic and dysplastic oral leukoplakias by use of optical spectroscopy,” Oral Oncol. 47(12), 1165–1170 (2011). [CrossRef] [PubMed]
  9. R. A. Schwarz, W. Gao, C. Redden Weber, C. Kurachi, J. J. Lee, A. K. El-Naggar, R. Richards-Kortum, A. M. Gillenwater, “Noninvasive evaluation of oral lesions using depth-sensitive optical spectroscopy,” Cancer 115(8), 1669–1679 (2009). [CrossRef] [PubMed]
  10. M. G. Müller, T. A. Valdez, I. Georgakoudi, V. Backman, C. Fuentes, S. Kabani, N. Laver, Z. Wang, C. W. Boone, R. R. Dasari, S. M. Shapshay, M. S. Feld, “Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,” Cancer 97(7), 1681–1692 (2003). [CrossRef] [PubMed]
  11. D. C. de Veld, M. Skurichina, M. J. Witjes, R. P. Duin, H. J. Sterenborg, J. L. Roodenburg, “Autofluorescence and diffuse reflectance spectroscopy for oral oncology,” Lasers Surg. Med. 36(5), 356–364 (2005). [CrossRef] [PubMed]
  12. N. Subhash, J. R. Mallia, S. S. Thomas, A. Mathews, P. Sebastian, J. Madhavan, “Oral cancer detection using diffuse reflectance spectral ratio R540/R575 of oxygenated hemoglobin bands,” J. Biomed. Opt. 11(1), 014018 (2006). [CrossRef] [PubMed]
  13. R. Choe, S. D. Konecky, A. Corlu, K. Lee, T. Durduran, D. R. Busch, S. Pathak, B. J. Czerniecki, J. Tchou, D. L. Fraker, A. Demichele, B. Chance, S. R. Arridge, M. Schweiger, J. P. Culver, M. D. Schnall, M. E. Putt, M. A. Rosen, A. G. Yodh, “Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography,” J. Biomed. Opt. 14(2), 024020 (2009). [CrossRef] [PubMed]
  14. G. Yu, T. Durduran, G. Lech, C. Zhou, B. Chance, E. R. Mohler, A. G. Yodh, “Time-dependent blood flow and oxygenation in human skeletal muscles measured with noninvasive near-infrared diffuse optical spectroscopies,” J. Biomed. Opt. 10(2), 024027 (2005). [CrossRef] [PubMed]
  15. T. Durduran, G. Yu, M. G. Burnett, J. A. Detre, J. H. Greenberg, J. Wang, C. Zhou, A. G. Yodh, “Diffuse optical measurement of blood flow, blood oxygenation, and metabolism in a human brain during sensorimotor cortex activation,” Opt. Lett. 29(15), 1766–1768 (2004). [CrossRef] [PubMed]
  16. V. T. Chang, P. S. Cartwright, S. M. Bean, G. M. Palmer, R. C. Bentley, N. Ramanujam, “Quantitative physiology of the precancerous cervix in vivo through optical spectroscopy,” Neoplasia 11(4), 325–332 (2009). [PubMed]
  17. H. W. Wang, J. K. Jiang, C. H. Lin, J. K. Lin, G. J. Huang, J. S. Yu, “Diffuse reflectance spectroscopy detects increased hemoglobin concentration and decreased oxygenation during colon carcinogenesis from normal to malignant tumors,” Opt. Express 17(4), 2805–2817 (2009). [CrossRef] [PubMed]
  18. B. W. Pogue, S. P. Poplack, T. O. McBride, W. A. Wells, K. S. Osterman, U. L. Osterberg, K. D. Paulsen, “Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast,” Radiology 218(1), 261–266 (2001). [PubMed]
  19. H. W. Wang, M. E. Putt, M. J. Emanuele, D. B. Shin, E. Glatstein, A. G. Yodh, T. M. Busch, “Treatment-induced changes in tumor oxygenation predict photodynamic therapy outcome,” Cancer Res. 64(20), 7553–7561 (2004). [CrossRef] [PubMed]
  20. H. W. Wang, J. C. Finlay, K. Lee, T. C. Zhu, M. E. Putt, E. Glatstein, C. J. Koch, S. M. Evans, S. M. Hahn, T. M. Busch, A. G. Yodh, “Quantitative comparison of tissue oxygen and motexafin lutetium uptake by ex vivo and noninvasive in vivo techniques in patients with intraperitoneal carcinomatosis,” J. Biomed. Opt. 12(3), 034023 (2007). [CrossRef] [PubMed]
  21. H. K. Roy, A. Gomes, V. Turzhitsky, M. J. Goldberg, J. Rogers, S. Ruderman, K. L. Young, A. Kromine, R. E. Brand, M. Jameel, P. Vakil, N. Hasabou, V. Backman, “Spectroscopic microvascular blood detection from the endoscopically normal colonic mucosa: biomarker for neoplasia risk,” Gastroenterology 135(4), 1069–1078 (2008). [CrossRef] [PubMed]
  22. C. Mărgăritescu, C. Simionescu, D. Pirici, L. Mogoantă, R. Ciurea, A. Stepan, “Immunohistochemical characterization of tumoral vessels in oral squamous cell carcinoma,” Rom. J. Morphol. Embryol. 49(4), 447–458 (2008). [PubMed]
  23. Z. J. Shang, J. R. Li, “Expression of endothelial nitric oxide synthase and vascular endothelial growth factor in oral squamous cell carcinoma: its correlation with angiogenesis and disease progression,” J. Oral Pathol. Med. 34(3), 134–139 (2005). [CrossRef] [PubMed]
  24. N. J. Beasley, R. Prevo, S. Banerji, R. D. Leek, J. Moore, P. van Trappen, G. Cox, A. L. Harris, D. G. Jackson, “Intratumoral lymphangiogenesis and lymph node metastasis in head and neck cancer,” Cancer Res. 62(5), 1315–1320 (2002). [PubMed]
  25. R. L. de Cicco, J. C. Watson, D. E. Bassi, S. Litwin, A. J. Klein-Szanto, “Simultaneous expression of furin and vascular endothelial growth factor in human oral tongue squamous cell carcinoma progression,” Clin. Cancer Res. 10(13), 4480–4488 (2004). [CrossRef] [PubMed]
  26. Y. K. Wong, C. J. Liu, P. C. Kwan, S. Y. Chao, “Microvascular density and vascular endothelial growth factor immunoreactivity as predictors of regional lymph node metastasis from betel-associated oral squamous cell carcinoma,” J. Oral Maxillofac. Surg. 61(11), 1257–1262 (2003). [CrossRef] [PubMed]
  27. M. Gandolfo, A. Keszler, H. Lanfranchi, M. E. Itoiz, “Increased subepithelial vascularization and VEGF expression reveal potentially malignant changes in human oral mucosa lesions,” Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 111(4), 486–493 (2011). [CrossRef] [PubMed]
  28. H. W. Wang, T. C. Zhu, M. E. Putt, M. Solonenko, J. Metz, A. Dimofte, J. Miles, D. L. Fraker, E. Glatstein, S. M. Hahn, A. G. Yodh, “Broadband reflectance measurements of light penetration, blood oxygenation, hemoglobin concentration, and drug concentration in human intraperitoneal tissues before and after photodynamic therapy,” J. Biomed. Opt. 10(1), 014004 (2005). [CrossRef] [PubMed]
  29. G. Yu, T. Durduran, C. Zhou, R. Cheng, and A. G. Yodh, “Near-infrared diffuse correlation spectroscopy for assessment of tissue blood flow,” in Handbook of Biomedical Optics, D. A. Boas, C. Pitris, and N. Ramanujam, eds. (CRC Press, Boca Raton, 2011), pp. 195–216.
  30. S. McGee, J. Mirkovic, V. Mardirossian, A. Elackattu, C. C. Yu, S. Kabani, G. Gallagher, R. Pistey, L. Galindo, K. Badizadegan, Z. Wang, R. Dasari, M. S. Feld, G. Grillone, “Model-based spectroscopic analysis of the oral cavity: impact of anatomy,” J. Biomed. Opt. 13(6), 064034 (2008). [CrossRef] [PubMed]
  31. D. J. Rohrbach, N. Rigual, E. Tracy, A. Kowalczewski, K. L. Keymel, M. T. Cooper, W. Mo, H. Baumann, B. W. Henderson, U. Sunar, “Interlesion differences in the local photodynamic therapy response of oral cavity lesions assessed by diffuse optical spectroscopies,” Biomed. Opt. Express 3(9), 2142–2153 (2012). [CrossRef] [PubMed]
  32. J. Carlile, K. Harada, R. Baillie, M. Macluskey, D. M. Chisholm, G. R. Ogden, S. L. Schor, A. M. Schor, “Vascular endothelial growth factor (VEGF) expression in oral tissues: possible relevance to angiogenesis, tumour progression and field cancerisation,” J. Oral Pathol. Med. 30(8), 449–457 (2001). [CrossRef] [PubMed]
  33. J. A. Nagy, L. F. Brown, D. R. Senger, N. Lanir, L. Van de Water, A. M. Dvorak, H. F. Dvorak, “Pathogenesis of tumor stroma generation: a critical role for leaky blood vessels and fibrin deposition,” Biochim. Biophys. Acta 948(3), 305–326 (1989). [PubMed]
  34. K. J. Davey, S. Perrier, G. Ohe, A. D. Gilbert, A. Bankfalvi, W. P. Saunders, S. L. Schor, A. M. Schor, “Assessment of vascularity as an index of angiogenesis in periradicular granulomas. Comparison with oral carcinomas and normal tissue counterparts,” Int. Endod. J. 41(11), 987–996 (2008). [CrossRef] [PubMed]
  35. F. Tanaka, Y. Otake, K. Yanagihara, Y. Kawano, R. Miyahara, M. Li, T. Yamada, N. Hanaoka, K. Inui, H. Wada, “Evaluation of angiogenesis in non-small cell lung cancer: comparison between anti-CD34 antibody and anti-CD105 antibody,” Clin. Cancer Res. 7(11), 3410–3415 (2001). [PubMed]
  36. D. Kademani, J. T. Lewis, D. H. Lamb, D. J. Rallis, J. R. Harrington, “Angiogenesis and CD34 expression as a predictor of recurrence in oral squamous cell carcinoma,” J. Oral Maxillofac. Surg. 67(9), 1800–1805 (2009). [CrossRef] [PubMed]
  37. U. K. Zätterström, E. Brun, R. Willén, E. Kjellén, J. Wennerberg, “Tumor angiogenesis and prognosis in squamous cell carcinoma of the head and neck,” Head Neck 17(4), 312–318 (1995). [CrossRef] [PubMed]
  38. K. Dellas, M. Bache, S. U. Pigorsch, H. Taubert, M. Kappler, D. Holzapfel, E. Zorn, H. J. Holzhausen, G. Haensgen, “Prognostic impact of HIF-1 α expression in patients with definitive radiotherapy for cervical cancer,” Strahlenther. Onkol. 184(3), 169–174 (2008). [CrossRef] [PubMed]
  39. K. Sakata, M. Someya, H. Nagakura, K. Nakata, A. Oouchi, M. Hareyama, M. Satoh, “A clinical study of hypoxia using endogenous hypoxic markers and polarographic oxygen electrodes,” Strahlenther. Onkol. 182(9), 511–517 (2006). [CrossRef] [PubMed]
  40. A. Mayer, M. Höckel, P. Vaupel, “Endogenous hypoxia markers: case not proven!” Adv. Exp. Med. Biol. 614, 127–136 (2008). [CrossRef] [PubMed]
  41. N. J. Beasley, R. Leek, M. Alam, H. Turley, G. J. Cox, K. Gatter, P. Millard, S. Fuggle, A. L. Harris, “Hypoxia-inducible factors HIF-1alpha and HIF-2alpha in head and neck cancer: relationship to tumor biology and treatment outcome in surgically resected patients,” Cancer Res. 62(9), 2493–2497 (2002). [PubMed]

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