Volume 5, Issue 2, Pages 60-69 (June 2010)

3 of 9

ABSTRACT

ABSTRACT + REFS

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Potential biomarkers for the cytologic diagnosis of oral squamous cell carcinoma

Received 3 February 2010; accepted 10 April 2010.

Unlike other deep cancers, oral squamous cell carcinoma (OSCC), which occurs in the oral cavity, is more easily monitored, and specimens for diagnosis are easier to collect. However, identifying reliable and sensitive markers for the early diagnosis and markers for identification of the recurrence of OSCC remains a challenge. This article mainly focused on reviewing recently identified potential biomarkers for a cytologic diagnosis during OSCC development. In addition, markers used in modern diagnostic technologies, including a sensitive labeling method and a photodynamic approach for cytologic diagnosis, are also described. Cytologic examinations using sensitive and specific biomarkers can improve the accuracy of the diagnosis. Hence, they can lead to appropriate treatment without delay and to the reduced recurrence of OSCC.

Key Words: biomarkers , cytologic diagnosis , oral squamous cell carcinoma

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References

1. 1 Kantola S , Parikka M , Jokinen K , et al. Prognostic factors in tongue cancer-relative importance of demographic, clinical and histopathological factors . Br J Cancer . 2000;83:614–619 . MEDLINE | CrossRef

2. 2 Zimmermann BG , Wong DT . Salivary mRNA targets for cancer diagnostics . Oral Oncol . 2008;44:425–429 . Abstract | Full Text | Full-Text PDF (108 KB) | CrossRef

3. 3 Mehrotra R , Hullmann M , Smeets R , Reichert TE , Driemel O . Oral cytology revisited . J Oral Pathol Med . 2009;38:161–166 . CrossRef

4. 4 Jones AC , Pink FE , Sandow PL , Stewart CM , Migliorati CA , Baughman RA . The Cytobrush Plus cell collector in oral cytology . Oral Surg Oral Med Oral Pathol . 1994;77:95–99 . MEDLINE | CrossRef

5. 5 Navone R , Burlo P , Pich A , et al. The impact of liquid-based oral cytology on the diagnosis of oral squamous dysplasia and carcinoma . Cytopathology . 2007;18:356–360 . CrossRef

6. 6 Mehrotra R , Singh MK , Pandya S , Singh M . The use of an oral brush biopsy without computer-assisted analysis in the evaluation of oral lesions: a study of 94 patients . Oral Surg Oral Med Oral Pathol Oral Radiol Endod . 2008;106:246–253 . Abstract | Full Text | Full-Text PDF (368 KB) | CrossRef

7. 7 Driemel O , Kunkel M , Hullmann M , et al. Diagnosis of oral squamous cell carcinoma and its precursor lesions . J Dtsch Dermatol Ges . 2007;5:1095–1100 . CrossRef

8. 8 Christian DC . Computer-assisted analysis of oral brush biopsies at an oral cancer screening program . J Am Dent Assoc . 2002;133:357–362 . MEDLINE

9. 9 Carvalho AL , Jeronimo C , Kim MM , et al. Evaluation of promoter hypermethylation detection in body fluids as a screening/diagnosis tool for head and neck squamous cell carcinoma . Clin Cancer Res . 2008;14:97–107 . CrossRef

10. 10 Pektas ZO , Keskin A , Gunhan O , Karslioglu Y . Evaluation of nuclear morphometry and DNA ploidy status for detection of malignant and premalignant oral lesions: quantitative cytologic assessment and review of methods for cytomorphometric measurements . J Oral Maxillofac Surg . 2006;64:628–635 . Abstract | Full Text | Full-Text PDF (248 KB)

11. 11 De Veld DC , Witjes MJ , Sterenborg HJ , Roodenburg JL . The status of in vivo autofluorescence spectroscopy and imaging for oral oncology . Oral Oncol . 2005;41:117–131 . Abstract | Full Text | Full-Text PDF (401 KB) | CrossRef

12. 12 Sharwani A , Jerjes W , Salih V , et al. Fluorescence spectros-copy combined with 5-aminolevulinic acid-induced proto-porphyrin IX fluorescence in detecting oral premalignancy . J Photochem Photobiol B . 2006;83:27–33 . MEDLINE | CrossRef

13. 13 O'Dwyer M , Day A , Padgett M , Ogden GR , McLaren S , Goodman CR . Detection of mucosal abnormalities in patients with oral cancer using a photodynamic technique: a pilot study . Br J Oral Maxillofac Surg . 2008;46:6–10 . Abstract | Full Text | Full-Text PDF (214 KB) | CrossRef

14. 14 Chang CJ , Wilder-Smith P . Topical application of photofrin for photodynamic diagnosis of oral neoplasms . Plast Reconstr Surg . 2005;115:1877–1886 . CrossRef

15. 15 Soukos NS , Hamblin MR , Keel S , Fabian RL , Deutsch TF , Hasan T . Epidermal growth factor receptor-targeted immunophotodiagnosis and photoimmunotherapy of oral precan-cer in vivo . Cancer Res . 2001;61:4490–4496 . MEDLINE

16. 16 Driemel O , Dahse R , Hakim SG , et al. Laminin-5 immunocytochemistry: a new tool for identifying dysplastic cells in oral brush biopsies . Cytopathology . 2007;18:348–355 . CrossRef

17. 17 Driemel O , Dahse R , Berndt A , et al. High-molecular tenascin-C as an indicator of atypical cells in oral brush biopsies . Clin Oral Investig . 2007;11:93–99 . MEDLINE | CrossRef

18. 18 Scott IS , Odell E , Chatrath P , et al. A minimally invasive im-munocytochemical approach to early detection of oral squamous cell carcinoma and dysplasia . Br J Cancer . 2006;94:1170–1175 . MEDLINE | CrossRef

19. 19 Kurokawa H , Zhang M , Matsumoto S , et al. Reduced syndecan-1 expression is correlated with the histological grade of malignancy at the deep invasive front in oral squamous cell carcinoma . J Oral Pathol Med . 2006;35:301–306 . MEDLINE | CrossRef

20. 20 Weng LP , Wu CC , Hsu BL , et al. Secretome-based identification of Mac-2 binding protein as a potential oral cancer marker involved in cell growth and motility . J Proteome Res . 2008;7:3765–3775 . CrossRef

21. 21 Hwang EY , Yu CH , Cheng SJ , Chang JY , Chen HM , Chiang CP . Decreased expression of Ep-CAM protein is significantly associated with the progression and prognosis of oral squa-mous cell carcinomas in Taiwan . J Oral Pathol Med . 2009;38:87–93 . CrossRef

22. 22 Yanamoto S , Kawasaki G , Yoshitomi I , Iwamoto T , Hirata K , Mizuno A . Clinicopathologic significance of EpCAM expression in squamous cell carcinoma of the tongue and its possibility as a potential target for tongue cancer gene therapy . Oral Oncol . 2007;43:869–877 . Abstract | Full Text | Full-Text PDF (980 KB) | CrossRef

23. 23 Lindberg P , Larsson A , Nielsen BS . Expression of plasmino-gen activator inhibitor-1, urokinase receptor and laminin γ-2 chain is an early coordinated event in incipient oral squamous cell carcinoma . Int J Cancer . 2006;118:2948–2956 . MEDLINE | CrossRef

24. 24 Bacchiocchi R , Rubini C , Pierpaoli E , et al. Prognostic value analysis of urokinase-type plasminogen activator receptor in oral squamous cell carcinoma: an immunohistochemical study . BMC Cancer . 2008;8:220 . CrossRef

25. 25 Vigneswaran N , Beckers S , Waigel S , et al. Increased EMMPRIN (CD 147) expression during oral carcinogenesis . Exp Mol Pathol . 2006;80:147–159 . MEDLINE | CrossRef

26. 26 Kuang YH , Chen X , Su J , et al. Proteome analysis of multi-drug resistance of human oral squamous carcinoma cells using CD147 silencing . J Proteome Res . 2008;7:4784–4791 . CrossRef

27. 27 Mack B , Gires O . CD44s and CD44v6 expression in head and neck epithelia . PLoS ONE . 2008;3:e3360 .

28. 28 Hagiwara S , Murakumo Y , Sato T , et al. Up-regulation of CD109 expression is associated with carcinogenesis of the squamous epithelium of the oral cavity . Cancer Sci . 2008;99:1916–1923 .

29. 29 Tsushima F , Tanaka K , Otsuki N , et al. Predominant expression of B7-H1 and its immunoregulatory roles in oral squa-mous cell carcinoma . Oral Oncol . 2006;42:268–274 . Abstract | Full Text | Full-Text PDF (387 KB) | CrossRef

30. 30 Pyo SW , Hashimoto M , Kim YS , et al. Expression of E-cadherin, P-cadherin and N-cadherin in oral squamous cell carcinoma: correlation with the clinicopathologic features and patient outcome . J Craniomaxillofac Surg . 2007;35:1–9 . Abstract | Full Text | Full-Text PDF (197 KB) | CrossRef

31. 31 Kaur G , Carnelio S , Rao N , Rao L . Expression of E-cadherin in primary oral squamous cell carcinoma and metastatic lymph nodes: an immunohistochemical study . Indian J Dent Res . 2009;20:71–76 . CrossRef

32. 32 Nagatsuka H , Hibi K , Gunduz M , et al. Various immuno-staining patterns of CD31, CD34 and endoglin and their relationship with lymph node metastasis in oral squamous cell carcinomas . J Oral Pathol Med . 2005;34:70–76 . MEDLINE | CrossRef

33. 33 Angiero F , Sordo RD , Dessy E , et al. Comparative analysis of c-erbB-2 (HER-2/neu) in squamous cell carcinoma of the tongue: does over-expression exist? And what is its correlation with traditional diagnostic parameters? . J Oral Pathol Med . 2008;37:145–150 . CrossRef

34. 34 Ravindranath NM , Shuler C . Expression of complement restriction factors (CD46, CD55 & CD59) in head and neck sq-uamous cell carcinomas . J Oral Pathol Med . 2006;35:560–567 . MEDLINE | CrossRef

35. 35 Atsumi N , Ishii G , Kojima M , Sanada M , Fujii S , Ochiai A . Podoplanin, a novel marker of tumor-initiating cells in human squamous cell carcinoma A431 . Biochem Biophys Res Commun . 2008;373:36–41 . CrossRef

36. 36 Martin-Villar E , Scholl FG , Gamallo C , et al. Characterization of human PA2.26 antigen (T1a-2, podoplanin), a small membrane mucin induced in oral squamous cell carcinomas . Int J Cancer . 2005;113:899–910 . MEDLINE | CrossRef

37. 37 Weise JB , Rudolph P , Heiser A , et al. LOXL4 is a selectively expressed candidate diagnostic antigen in head and neck cancer . Eur J Cancer . 2008;44:1323–1331 . Abstract | Full Text | Full-Text PDF (1519 KB) | CrossRef

38. 38 Tseng MY , Liu SY , Chen HR , et al. Serine protease inhibitor (SERPIN) B1 promotes oral cancer cell motility and is over-expressed in invasive oral squamous cell carcinoma . Oral Oncol . 2009;45:771–776 . Abstract | Full Text | Full-Text PDF (1990 KB) | CrossRef

39. 39 Leung KW , Tsai CH , Hsiao M , et al. Pin1 overexpression is associated with poor differentiation and survival in oral squamous cell carcinoma . Oncol Rep . 2009;21:1097–1104 .

40. 40 Liu SY , Chang LC , Pan LF , Hung YJ , Lee CH , Shieh YS . Clinicopathologic significance of tumor cell-lined vessel and microenvironment in oral squamous cell carcinoma . Oral Oncol . 2008;44:277–285 . Abstract | Full Text | Full-Text PDF (1258 KB) | CrossRef

41. 41 Lin PY , Yu CH , Wang JT , et al. Expression of hypoxia-inducible factor-1a is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan . J Oral Pathol Med . 2008;37:18–25 . CrossRef

42. 42 Liang X , Yang D , Hu J , Hao X , Gao J , Mao Z . Hypoxia inducible factor-a expression correlates with vascular endothelial growth factor-C expression and lymphangiogenesis/angiogenesis in oral squamous cell carcinoma . Anticancer Res . 2008;28:1659–1666 .

43. 43 Lin CY , Jeng YM , Chou HY , et al. Nuclear localization of an-nexin A1 is a prognostic factor in oral squamous cell carcinoma . J Surg Oncol . 2008;97:544–550 . CrossRef

44. 44 Chuang FH , Hsue SS , Wu CW , Chen YK . Immunohistochemical expression of RANKL, RANK, and OPG in human oral squa-mous cell carcinoma . J Oral Pathol Med . 2009;38:753–758 . CrossRef

45. 45 Lu CF , Huang CS , Tjiu JW , Chiang CP . Infiltrating macrophage count: a significant predictor for the progression and prognosis of oral squamous cell carcinomas in Taiwan . Head Neck . 2010;32:18–25 .

46. 46 Costea DE , Tsinkalovsky O , Vintermyr OK , Johannessen AC , Mackenzie IC . Cancer stem cells-new and potentially important targets for the therapy of oral squamous cell carcinoma . Oral Dis . 2006;12:443–454 . CrossRef

47. 47 Chiou SH , Yu CC , Huang CY , et al. Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma . Clin Cancer Res . 2008;14:4085–4095 . CrossRef

48. 48 Scheifele C , Schmidt-Westhausen AM , Dietrich T , Reichart PA . The sensitivity and specificity of the OralCDx technique: evaluation of 103 cases . Oral Oncol . 2004;40:824–828 . Abstract | Full Text | Full-Text PDF (167 KB) | CrossRef

49. 49 Sciubba JJ . Improving detection of precancerous and cancerous oral lesions: computer-assisted analysis of the oral brush biopsy. U.S. Collaborative OralCDx Study Group . J Am Dent Assoc . 1999;130:1445–1457 . MEDLINE

50. 50 Remmerbach TW , Weidenbach H , Hemprich A , Bocking A . Earliest detection of oral cancer using non-invasive brush biopsy including DNA-image-cytometry: report on four cases . Anal Cell Pathol . 2003;25:159–166 . MEDLINE

51. 51 Remmerbach TW , Weidenbach H , Pomjanski N , et al. Cytologic and DNA-cytometric early diagnosis of oral cancer . Anal Cell Pathol . 2001;22:211–221 . MEDLINE

52. 52 Sudbo J , Kildal W , Risberg B , Koppang HS , Danielsen HE , Reith A . DNA content as a prognostic marker in patients with oral leukoplakia . N Engl J Med . 2001;344:1270–1278 . MEDLINE | CrossRef

53. 53 Maraki D , Becker J , Boecking A . Cytologic and DNA-cytometric very early diagnosis of oral cancer . J Oral Pathol Med . 2004;33:398–404 . MEDLINE | CrossRef

54. 54 Harris DM , Werkhaven J . Endogenous porphyrin fluorescence in tumors . Lasers Surg Med . 1987;7:467–472 . MEDLINE | CrossRef

55. 55 Harris DM , Hill JH , Werkhaven JA , Applebaum EL , Lobraico RV , Waldow SM . Porphyrin fluorescence and photosensitization in head and neck cancer . Arch Otolaryngol Head Neck Surg . 1986;112:1194–1199 . MEDLINE

56. 56 Sharma S , Jajoo A , Dube A . 5-Aminolevulinic acid-induced protoporphyrin-IX accumulation and associated photo-toxicity in macrophages and oral cancer cell lines . J Photochem Photobiol B . 2007;88:156–162 . CrossRef

57. 57 Sharwani A , Jerjes W , Hopper C , et al. Photodynamic therapy down-regulates the invasion promoting factors in human oral cancer . Arch Oral Biol . 2006;51:1104–1111 . Abstract | Full Text | Full-Text PDF (350 KB) | CrossRef

58. 58 Franz M , Hansen T , Borsi L , et al. A quantitative co-localization analysis of large unspliced tenascin-C(L) and laminin-5/γ2-chain in basement membranes of oral squamous cell carcinoma by confocal laser scanning microscopy . J Oral Pathol Med . 2007;36:6–11 . MEDLINE | CrossRef

59. 59 Chen C , Mendez E , Houck J , et al. Gene expression profiling identifies genes predictive of oral squamous cell carcinoma . Cancer Epidemiol Biomarkers Prev . 2008;17:2152–2162 . CrossRef

60. 60 Driemel O , Kosmehl H , Rosenhahn J , et al. Expression analysis of extracellular matrix components in brush biopsies of oral lesions . Anticancer Res . 2007;27:1565–1570 . MEDLINE

61. 61 Franz M , Hansen T , Richter P , et al. Complex formation of the laminin-5 γ2 chain and large unspliced tenascin-C in oral squamous cell carcinoma in vitro and in situ: implications for sequential modulation of extracellular matrix in the invasive tumor front . Histochem Cell Biol . 2006;126:125–131 . MEDLINE | CrossRef

62. 62 Mendez E , Houck JR , Doody DR , et al. A genetic expression profile associated with oral cancer identifies a group of patients at high risk of poor survival . Clin Cancer Res . 2009;15:1353–1361 . CrossRef

63. 63 Chuang WY , Yeh CJ , Wu YC , et al. Tumor cell expression of podoplanin correlates with nodal metastasis in esophageal sq-uamous cell carcinoma . Histol Histopathol . 2009;24:1021–1027 .

64. 64 Ishikawa T , Nakashiro K , Klosek SK , et al. Hypoxia enhances CXCR4 expression by activating HIF-1 in oral squamous cell carcinoma . Oncol Rep . 2009;21:707–712 .

65. 65 Uehara M , Sano K , Ikeda H , Nonaka M , Asahina I . Hypoxia-inducible factor 1a in oral squamous cell carcinoma and its relation to prognosis . Oral Oncol . 2009;45:241–246 . Abstract | Full Text | Full-Text PDF (170 KB) | CrossRef

66. 66 Kurokawa T , Miyamoto M , Kato K , et al. Overexpression of hypoxia-inducible-factor 1a (HIF-1a) in oesophageal squa-mous cell carcinoma correlates with lymph node metastasis and pathologic stage . Br J Cancer . 2003;89:1042–1047 . MEDLINE | CrossRef

67. 67 Faria PC , Sena AA , Nascimento R , et al. Expression of an-nexin A1 mRNA in peripheral blood from oral squamous cell carcinoma patients . Oral Oncol . 2010;46:25–30 . Abstract | Full Text | Full-Text PDF (347 KB) | CrossRef

68. 68 Koike H , Uzawa K , Nakashima D , et al. Identification of differentially expressed proteins in oral squamous cell carcinoma using a global proteomic approach . Int J Oncol . 2005;27:59–67 . MEDLINE

69. 69 Nomura H , Uzawa K , Yamano Y , et al. Down-regulation of plasma membranous Annexin A1 protein expression in pre-malignant and malignant lesions of the oral cavity: correlation with epithelial differentiation . J Cancer Res Clin Oncol . 2009;135:943–949 . CrossRef

70. 70 Zhang L , Yang X , Zhong LP , et al. Decreased expression of Annexin A1 correlates with pathologic differentiation grade in oral squamous cell carcinoma . J Oral Pathol Med . 2009;38:362–370 . CrossRef

71. 71 Graziano A , d'Aquino R , Tirino V , Desiderio V , Rossi A , Pirozzi G . The stem cell hypothesis in head and neck cancer . J Cell Biochem . 2008;103:408–412 . CrossRef

72. 72 Chen PC , Kuo C , Pan CC , Chou MY . Risk of oral cancer associated with human papillomavirus infection, betel quid chewing, and cigarette smoking in Taiwan-an integrated molecular and epidemiological study of 58 cases . J Oral Pathol Med . 2002;31:317–322 . MEDLINE | CrossRef

73. 73 Chen PC , Pan CC , Kuo C , Lin CP . Risk of oral nonmalignant lesions associated with human papillomavirus infection, betel quid chewing, and cigarette smoking in Taiwan: an integrated molecular and epidemiologic study . Arch Pathol Lab Med . 2006;130:57–61 .

74. 74 Tsai KY , Su CC , Lin YY , Chung JA , Lian IB . Quantification of betel quid chewing and cigarette smoking in oral cancer patients . Community Dent Oral Epidemiol . 2009;37:555–561 . CrossRef

75. 75 Chen YJ , Chang JT , Liao CT , et al. Head and neck cancer in the betel quid chewing area: recent advances in molecular carcinogenesis . Cancer Sci . 2008;99:1507–1514 . CrossRef

76. 76 Chen CL , Chi CW , Liu TY . Hydroxyl radical formation and oxidative DNA damage induced by areca quid in vivo . J Toxicol Environ Health A . 2002;65:327–336 . MEDLINE | CrossRef

77. 77 Yang SC , Lin SC , Chiang WF , Yen CY , Lin CH , Liu SY . Areca nut extract treatment elicits the fibroblastoid morphological changes, actin re-organization and signaling activation in oral keratinocytes . J Oral Pathol Med . 2003;32:600–605 . MEDLINE | CrossRef

78. 78 Lee CH , Liu SY , Lin MH , et al. Upregulation of matrix met-alloproteinase-1 (MMP-1) expression in oral carcinomas of betel quid (BQ) users: roles of BQ ingredients in the acceleration of tumour cell motility through MMP-1 . Arch Oral Biol . 2008;53:810–818 . Abstract | Full Text | Full-Text PDF (1379 KB) | CrossRef

79. 79 Liu SY , Liu YC , Huang WT , Huang GC , Chen TC , Lin MH . Up-regulation of matrix metalloproteinase-8 by betel quid extract and arecoline and its role in 2D motility . Oral Oncol . 2007;43:1026–1033 . Abstract | Full Text | Full-Text PDF (938 KB) | CrossRef

80. 80 Chang KW , Kao SY , Tzeng RJ , et al. Multiple molecular alterations of FHIT in betel-associated oral carcinoma . J Pathol . 2002;196:300–306 . MEDLINE | CrossRef

81. 81 Chang KC , Su IJ , Tsai ST , Shieh DB , Jin YT . Pathological features of betel quid-related oral epithelial lesions in Taiwan with special emphasis on the tumor progression and human papillomavirus association . Oncology . 2002;63:362–369 .

82. 82 Chen IH , Chang JT , Liao CT , Wang HM , Hsieh LL , Cheng AJ . Prognostic significance of EGFR and Her-2 in oral cavity cancer in betel quid prevalent area cancer prognosis . Br J Cancer . 2003;89:681–686 . MEDLINE | CrossRef

83. 83 Chen CH , Lin YS , Lin CC , Yang YH , Ho YP , Tsai CC . Elevated serum levels of a c-erbB-2 oncogene product in oral squa-mous cell carcinoma patients . J Oral Pathol Med . 2004;33:589–594 . MEDLINE | CrossRef

84. 84 Wong YK , Liu CJ , Kwan PC , Chao SY . 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 . 2003;61:1257–1262 . Abstract | Full Text | Full-Text PDF (934 KB) | CrossRef

85. 85 Su TR , Chang KL , Lee CH , Chen CH , Yang YH , Shieh TY . Expression of tumor necrosis factor-a and its soluble receptors in betel-quid-chewing patients at different stages of treatment for oral squamous cell carcinoma . Oral Oncol . 2004;40:804–810 . Abstract | Full Text | Full-Text PDF (182 KB) | CrossRef

86. 86 Chen JY , Hung CC , Huang KL , et al. Src family kinases mediate betel quid-induced oral cancer cell motility and could be a biomarker for early invasion in oral squamous cell carcinoma . Neoplasia . 2008;10:1393–1401 .

87. 87 Tan DJ , Chang J , Chen WL , et al. Somatic mitochondrial DNA mutations in oral cancer of betel quid chewers . Ann N Y Acad Sci . 2004;1011:310–316 . MEDLINE | CrossRef

88. 88 Kao SY , Tu HF , Chang KW , Chang CS , Yang CC , Lin SC . The retinoic acid receptor-β (RAR-β) mRNA expression in the oral squamous cell carcinoma associated with betel quid use . J Oral Pathol Med . 2002;31:220–226 . MEDLINE | CrossRef

89. 89 Tsai ST , Jin YT , Tsai WC , et al. S100A2, a potential marker for early recurrence in early-stage oral cancer . Oral Oncol . 2005;41:349–357 . Abstract | Full Text | Full-Text PDF (199 KB) | CrossRef

90. 90 Kao SY , Wu CH , Lin SC , et al. Genetic polymorphism of cy-tochrome P4501A1 and susceptibility to oral squamous cell carcinoma and oral precancer lesions associated with smoking/betel use . J Oral Pathol Med . 2002;31:505–511 . MEDLINE | CrossRef

91. 91 Chang KW , Lee TC , Yeh WI , et al. Polymorphism in heme oxygenase-1 (HO-1) promoter is related to the risk of oral squamous cell carcinoma occurring on male areca chewers . Br J Cancer . 2004;91:1551–1555 . MEDLINE | CrossRef

92. 92 Lin SC , Liu CJ , Yeh WI , Lui MT , Chang KW , Chang CS . Functional polymorphism in NFKB1 promoter is related to the risks of oral squamous cell carcinoma occurring on older male areca (betel) chewers . Cancer Lett . 2006;243:47–54 . Abstract | Full Text | Full-Text PDF (144 KB) | CrossRef

93. 93 Lin SC , Chen YJ , Kao SY , et al. Chromosomal changes in betel-associated oral squamous cell carcinomas and their relationship to clinical parameters . Oral Oncol . 2002;38:266–273 . Abstract | Full Text | Full-Text PDF (144 KB) | CrossRef

94. 94 Liu HS , Lu HH , Lui MT , et al. Detection of copy number amplification of cyclin D1 (CCND1) and cortactin (CTTN) in oral carcinoma and oral brushed samples from areca chew-ers . Oral Oncol . 2009;45:1032–1036 . Abstract | Full Text | Full-Text PDF (1095 KB) | CrossRef

95. 95 Yen CY , Liu SY , Chen CH , et al. Combinational polymorphisms of four DNA repair genes XRCC1, XRCC2, XRCC3, and XRCC4 and their association with oral cancer in Taiwan . J Oral Pathol Med . 2008;37:271–277 . CrossRef

96. 96 Chiu CF , Tsai MH , Tseng HC , et al. A novel single nucleotide polymorphism in XRCC4 gene is associated with oral cancer susceptibility in Taiwanese patients . Oral Oncol . 2008;44:898–902 . Abstract | Full Text | Full-Text PDF (215 KB) | CrossRef

97. 97 Chiang SL , Chen PH , Lee CH , et al. Up-regulation of inflammatory signalings by areca nut extract and role of cyclooxy genase-2-1195G > a polymorphism reveal risk of oral cancer . Cancer Res . 2008;68:8489–8498 . CrossRef

98. 98 Chen JY , Chang YL , Yu YC , et al. Specific induction of the high-molecular-weight microtubule-associated protein 2 (hmw-MAP2) by betel quid extract in cultured oral keratinocytes: clinical implications in betel quid-associated oral squamous cell carcinoma (OSCC) . Carcinogenesis . 2004;25:269–276 . MEDLINE | CrossRef

99. 99 Liu SA , Tsai WC , Wong YK , et al. Nutritional factors and survival of patients with oral cancer . Head Neck . 2006;28:998–1007 . MEDLINE | CrossRef

100. 100 Su CC , Yang HF , Huang SJ , Lian Ie B . Distinctive features of oral cancer in Changhua County: high incidence, buccal mucosa preponderance, and a close relation to betel quid chewing habit . J Formos Med Assoc . 2007;106:225–233 . Abstract | Full-Text PDF (148 KB) | CrossRef

101. 101 Chen CJ , You SL , Lin LH , Hsu WL , Yang YW . Cancer epidemiology and control in Taiwan: a brief review . Jpn J Clin Oncol . 2002;32(Suppl):S66–S81 .

102. 102 Wen CP , Tsai SP , Cheng TY , et al. Uncovering the relation between betel quid chewing and cigarette smoking in Taiwan . Tob Control . 2005;14(Suppl 1):i16–i22 . CrossRef

103. 103 Chen PH , Ko YC , Yang YH , et al. Important prognostic factors of long-term oropharyngeal carcinoma survivors in Taiwan . Oral Oncol . 2004;40:847–855 . Abstract | Full Text | Full-Text PDF (341 KB) | CrossRef

104. 104 Lee CH , Ko YC , Huang HL , et al. The precancer risk of betel quid chewing, tobacco use and alcohol consumption in oral leukoplakia and oral submucous fibrosis in southern Taiwan . Br J Cancer . 2003;88:366–372 . MEDLINE | CrossRef

105. 105 Kuo MY , Lin CY , Hahn LJ , Cheng SJ , Chiang CP . Expression of cyclin D1 is correlated with poor prognosis in patients with areca quid chewing-related oral squamous cell carcinomas in Taiwan . J Oral Pathol Med . 1999;28:165–169 . MEDLINE | CrossRef

106. 106 Chiang CP , Huang JS , Wang JT , et al. Expression of p53 protein correlates with decreased survival in patients with areca quid chewing and smoking-associated oral squamous cell carcinomas in Taiwan . J Oral Pathol Med . 1999;28:72–76 . MEDLINE | CrossRef

107. 107 Chen HM , Yen-Ping Kuo M , Lin KH , Lin CY , Chiang CP . Expression of cyclin A is related to progression of oral squa-mous cell carcinoma in Taiwan . Oral Oncol . 2003;39:476–482 . Abstract | Full Text | Full-Text PDF (348 KB) | CrossRef

108. 108 Lin CY , Hung HC , Kuo RC , Chiang CP , Kuo MY . Survivin expression predicts poorer prognosis in patients with areca quid chewing-related oral squamous cell carcinoma in Taiwan . Oral Oncol . 2005;41:645–654 . Abstract | Full Text | Full-Text PDF (287 KB)

109. 109 Chen HH , Yu CH , Wang JT , et al. Expression of human telom-erase reverse transcriptase (hTERT) protein is significantly associated with the progression, recurrence and prognosis of oral squamous cell carcinoma in Taiwan . Oral Oncol . 2007;43:122–129 . Abstract | Full Text | Full-Text PDF (928 KB) | CrossRef

110. 110 Tsai TC , Yu CH , Cheng SJ , Liu BY , Chen HM , Chiang CP . Expression of RCAS1 is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan . Oral Oncol . 2008;44:759–766 . Abstract | Full Text | Full-Text PDF (947 KB) | CrossRef

111. 111 Chang HH , Chiang CP , Hung HC , Lin CY , Deng YT , Kuo MY . Histone deacetylase 2 expression predicts poorer prognosis in oral cancer patients . Oral Oncol . 2009;45:610–614 . Abstract | Full Text | Full-Text PDF (433 KB) | CrossRef

112. 112 Kuo MY , Chang HH , Hahn LJ , Wang JT , Chiang CP . Elevated ras p21 expression in oral premalignant lesions and squa-mous cell carcinoma in Taiwan . J Oral Pathol Med . 1995;24:255–260 . MEDLINE | CrossRef

113. 113 Chen YS , Wang JT , Chang YF , et al. Expression of hepatocyte growth factor and c-met protein is significantly associated with the progression of oral squamous cell carcinoma in Taiwan . J Oral Pathol Med . 2004;33:209–217 . MEDLINE | CrossRef

114. 114 Chiu CH , Chang JYF , Wang YP , et al. Expression of erythropoietin and its receptor in oral squamous cell carcinomas . J Dent Sci . 2008;3:38–48 .

115. 115 Lin YH , Hung HY , Yu CH , et al. Expression of p34cdc2 in oral epithelial dysplasia and oral squamous cell carcinoma . J Dent Sci . 2008;3:125–132 .

116. 116 Chang CC , Yu CH , Hung HY , et al. Expression of cellular inhibitor of apoptosis protein 1 in oral squamous cell carcinoma and precancerous lesions . J Dent Sci . 2008;3:83–92 .

117. 117 Huang JS , Ho TJ , Chiang CP , Kok SH , Kuo YS , Kuo MY . MDM2 expression in areca quid chewing-associated oral squamous cell carcinomas in Taiwan . J Oral Pathol Med . 2001;30:53–58 . MEDLINE

118. 118 Kuo MY , Hsu HY , Kok SH , et al. Prognostic role of p27Kip1 expression in oral squamous cell carcinoma in Taiwan . Oral Oncol . 2002;38:172–178 . Abstract | Full Text | Full-Text PDF (197 KB) | CrossRef

119. 119 Yu CH , Chen HH , Wang JT , et al. Nuclear expression of metastasis-associated protein 1 (MTA1) is inversely related to progression of oral squamous cell carcinoma in Taiwan . J Dent Sci . 2007;2:1–10 .

120. 120 Yen-Ping Kuo M , Huang JS , Kok SH , Kuo YS , Chiang CP . Prognostic role of p21WAF1 expression in areca quid chewing and smoking-associated oral squamous cell carcinoma in Taiwan . J Oral Pathol Med . 2002;31:16–22 . MEDLINE

121. 121 Chang HH , Kuo MY , Cheng SJ , Chiang CP . Expression of BCL10 is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan . Oral Oncol . 2009;45:589–593 . Abstract | Full Text | Full-Text PDF (310 KB) | CrossRef

a Graduate Institute of Biomedical Materials and Engineering, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan

b School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan

c Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan

Corresponding author: Graduate Institute of Biomedical Materials and Engineering, College of Oral Medicine, Taipei Medical University, 250 Wu-Xing Street, Taipei 11042, Taiwan

PII: S1991-7902(10)60010-4

doi:10.1016/S1991-7902(10)60010-4

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