Oral field cancerization: Carcinogen-induced independent events or micrometastatic deposits?

Cancer Epidemiology Biomarkers and Prevention

Volumn 9, Issue 3, 2000, Pages 249-256

  Van Oijen, Monique G C T ^a   Slootweg, Pieter J ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIN D1; CYTOKERATIN; EPIDERMAL GROWTH FACTOR RECEPTOR; GLUTATHIONE TRANSFERASE; PROTEIN BCL 2; PROTEIN P53; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE PHOSPHATASE;

ALCOHOL CONSUMPTION; ANEUPLOIDY; CANCER RISK; CELL MIGRATION; CHROMOSOME ABERRATION; DISEASE ASSOCIATION; HEAD CANCER; HUMAN; METASTASIS; NECK CANCER; PRECANCER; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; RISK FACTOR; SMOKING; SQUAMOUS CELL CARCINOMA;

CARCINOGENS; CARCINOMA, SQUAMOUS CELL; CELL TRANSFORMATION, NEOPLASTIC; GENE EXPRESSION REGULATION, NEOPLASTIC; HEAD AND NECK NEOPLASMS; HUMANS; MUCOUS MEMBRANE; NEOPLASM METASTASIS; NEOPLASMS, SECOND PRIMARY; PRECANCEROUS CONDITIONS;

EID: 0034022890     PISSN: 10559965     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (96)

1. Parkin, D. M., Pisani, P., and Ferlay, J. Estimates of the worldwide frequency of 25 major cancers in 1990. Int. J. Cancer, 80: 827-841, 1999.
2. Boring, C. C., Squires, T. S., and Tong, T. Cancer statistics. CA Cancer J. Clin., 42: 19-38, 1992.
3. La Vecchia, C., Tavani, A., Franceshi, S., Levi, F., Corrao, G., and Negri, E. Epidemiology and prevention of oral cancer. Oral Oncol., 33: 302-312, 1997.
4. Pindborg, J. J. Control of oral cancer in developing countries. Bull. WHO, 62: 817-824, 1984.
5. Wight, A. J., and Ogden, G. R. Possible mechanisms by which alcohol may influence the development of oral cancer. A review. Oral Oncol., 14: 441-447, 1998.
6. Andre, K., Schraub, S., Mercier, M., and Bontemps, P. Role of alcohol and tobacco in the aetiology of head and neck cancer, a case-control study in the Doubs region of France. Oral Oncol. Eur. J. Cancer, 31B: 301-309, 1995.
7. Woolgar, J. A., Rogers, S., West, C. R., Errington, R. D., Brown, J. S., and Vaughan, E. D. Survival and patterns of recurrence in 200 oral cancer patients treated by radical surgery and neck dissection. Oral Oncol., 35: 257-265, 1999.
8. Day, G. L., Blot, W. J., Shore, R. E., Day, G. L., Blot, W. J., Shore, R. E., McLaughlin, J. K., Austin, D. F., Greenberg, R. S., Liff, J. M., Preston-Martin, S., Sarkar, S., and Schoenberg, J. B. Second cancers following oral and pharyngeal cancers: role of tobacco and alcohol. J. Natl. Cancer Inst, 86: 131-137, 1994.
9. Cianfrigkia, F., Di Gregorio, D. A., and Manieri, A. Multiple primary tumours in patients with oral squamous cell carcinoma. Oral Oncol., 35: 157-163, 1999.
10. Dhooge, I. J., De Vos, M., and Van Cauwenberge, P. B. Multiple primary malignant tumors in patients with head and neck cancer: results of a prospective study and future perspectives. Laryngoscope, 108: 250-256, 1998.
11. Slaughter, D. P., Southwick, H. W., and Smejkal, W. "Field cancerization" in oral stratified squamous epithelium. Cancer (Phila.), 6: 963-968, 1953.
12. Califano, J., van der Riet, P., Westra, W., Nawroz, H., Clayman, G., Piantadosi, S., Corio, R., Lee, D., Greenberg, B., Koch, W., and Sidransky, D. Genetic progression model for head and neck cancer: implications for field cancerization. Cancer Res., 56: 2488-2492, 1996.
13. Bedi, G. C., Westra, W. H., Gabrielson, E., Koch, W., and Sidransky, D. Multiple head and neck tumors: evidence for a common clonal origin. Cancer Res., 56: 2484-2487, 1996.
14. Partridge, M., Emilion, G., Pateromichelakis, S., Phillips, E., and Langdon, J. Field Cancerisation of the oral cavity: comparison of the spectrum of molecular alterations in cases presenting with both dysplastic and malignant lesions. Oral Oncol., 33: 332-337, 1997.
15. Nieburgs, H. E., Herman, B. E., and Reisman, H. Buccal cell changes in patients with malignant tumours. Lab. Invest., 11: 80-88, 1962.
16. Incze, J., Vaughan, C. W., Lui, P., Strong, M. S., and Kulapaditharom, B. Premalignant changes in normal appearing epithelium in patients with squamous cell carcinoma of the upper aerodigestive tract. Am. J. Surg., 144: 401-405, 1982.
17. Ogden, G. R., Cowpe, J. G., and Green, M. W. The effect of distant malignancy upon quantitative cytologic assessment of normal oral mucosa. Cancer (Phila.), 65: 477-480, 1990.
18. Ogden, G. R., Cowpe, J. G., and Green, M. W. Detection of field change in oral cancer using oral exfoliative cytologic study. Cancer (Phila.), 68: 1611-1615, 1991.
19. Ogden, G. R., Cowpe, J. G., and Green, M. W. Quantitative exfoliative cytology of normal buccal mucosa: effect of smoking. J. Oral Pathol. Med., 19: 53-55, 1990.
20. Högmo, A., Lindskog, S., Lindholm, J., Kuylenstierna, R., Auer, G., and Munck-Wikland, E. Preneoplastic oral lesions: the clinical value of image cytometry DNA analysis, p53 and p21/WAF1 expression. Anticancer Res., 18: 3645-3650, 1998.
21. Hittelman, W. N., Kim, H. J., Lee, J. S., Shin, D. M., Lippman, S. M., Kim, J., Ro, J. Y., and Hong, W. K. Detection of instability of tissue fields at risk: in situ hybridization. J. Cell. Biochem. Suppl., 25: 57-62, 1996.
22. Ai, H., Barrera, J., Pan, Z., Meyers, A. D., and Varella-Garcia, M. Identification of individuals at high risk for head and neck carcinogenesis using chromosome aneuploidy detected by fluorescence in situ hybridization. Mutat. Res., 439: 223-232, 1999.
23. Voravud, N., Shin, D. M., Ro, J. Y., Lee, J. S., Hong, W. K., and Hittelman, W. N. Increased polysomies of chromosomes 7 and 17 during head and neck multistage tumorigenesis. Cancer Res., 53: 2874-2883, 1993.
24. Choi, G. C., and Chung, K. C. Polysomies of chromosomes 7 and 17 in head and neck squamous cell carcinomas. Arch. Otolaryngol. Head Neck Surg., 122: 1062-1067, 1996.
25. Van Oijen, M. G. C. T., Poorts, L. K., and Slootweg, P. J. Mucosal changes in head and neck cancer. Incipient tumors or micrometastases? J. Cancer Res., Clin. Oncol., 125 (Suppl. 2): S105, 1999.
26. Lee, N. K., Ye, Y.-W., Li, X., Schweitzer, C., and Nisen, P. D. Allelic loss on chromosome 13 can preceed histological changes in head and neck cancer. Int. J. Oncol., 5: 205-210, 1994.
27. Moll, R., Franke, W. W., and Schiller, D. L. The catalogue of human cytokeratin: pattern of expression in normal epithelia, tumours and culture cells. Cell, 31: 11-24, 1982.
28. Van der Velden, L. A., Schaafsma, E., Manni, J. J., Ramaekers, F. C. S., and Kuypers. W. Cytokeratin expression in normal and (pre)malignant head and neck epithelia: an overview. Head Neck, 15: 133-146, 1993.
29. Lindberg, K., and Rheinwald, J. G. Suprabasal 40kd keratin (K19) expression as an immunohistologic marker of premalignancy in oral epithelium. Am. J. Pathol., 134: 89-98, 1989.
30. Copper, M. P., Braakhuis, B. J. M., de Vries, N., van dongen, G. A. M. S., Nauta, J. J. P., and Snow, G. B. A panel of biomarkers of carcinogenesis of the upper aerodigestive tract as potential intermediate endpoints in chemoprevention trials. Cancer (Phila.), 71: 825-830, 1993.
31. Ogden, G. R., Lane, E. B., Hopwood, D. V., and Chisholm, D. M. Evidence for field change in oral cancer based on cytokeratin expression. Br. J. Cancer, 67: 1324-1330, 1993.
32. Bongers, V., Snow, G. B., de Vries, N., and Braakhuis, B. J. M. Potential early markers of carcinogenesis in the mucosa of the head and neck using exfoliative cytology. J. Pathol., 178: 284-289, 1996.
33. Bosch, F. X., Ouhayoun, J. P., Bader, B. L., Collin, C., Grund, C., Lee, I., and Franke, W. W. Extensive changes in cytokeratins expression patterns in pathologically affected human gingiva. Virchows Arch. B Cell Pathol., 58: 59-77, 1989.
34. Dabelsteen, E., Mandel, U., and Clausen, H. Cell surface carbohydrates are markers of differentiation in human oral epithelium. Crit. Rev. Oral Biol. Med., 2: 419-426, 1991.
35. Hosowaka, Y., and Arnold, A. Cyclin D1/PRAD1 as a central target in oncogenesis. J. Lab. Clin. Med., 127: 246-255, 1996.
36. Izzo, J. G., Papadimitrakopoulou, V. A., Li, X. Q., Ibarguen, H., Lee, J. S., Ro, J. Y., El-Naggar, A., Hong, W. K., and Hittelman, W. N. Dysregulated cyclin D1 expression early in head and neck tumorigenesis: in vivo evidence for an association with subsequent gene amplification. Oncogene, 17: 2313-2322, 1998.
37. 1 regulation in human head and neck cancer. Cancer Res., 55: 949-956, 1995.
38. King, L. E. What does the epidermal growth factor do and how does it do it? J. Invest. Dermatol., 84: 165-169, 1985.
39. Eisbruch, A., Blick, M., Lee, J. S., Sacks, P. G., and Gutterman, J. Analysis of the epidermal growth factor receptor gene in fresh human head and neck tumors. Cancer Res., 47: 3603-3605, 1987.
40. Grandis, J. R., and Tweardy, D. J. Elevated levels of transforming growth factor α and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Cancer Res., 53: 3579-3584, 1993.
41. Christensen, M. E., Engbaek, F., Therkildsen, M. H., Bretlau, P., and Nexo, E. A sensitive enzyme-linked immunosorbent assay used for quantitation of epidermal growth factor receptor protein in head and neck carcinomas: evaluation, interpretations and limitations. Br. J. Cancer, 72: 1487-1493, 1995.
42. Shin, D. M., Ro, J. Y., Hong, W. K., and Hittelman, W. N. Dysregulation of epidermal growth factor receptor expression in premalignant lesions during head and neck tumorgenesis. Cancer Res., 54: 3153-3159, 1994.
43. Van Oijen, M. G. C. T., Rijksen, G., ten Broek, F. W., and Slootweg, P. J. Increased expression of epidermal growth factor receptor in normal epithelium adjacent to head and neck carcinomas independent of tobacco and alcohol abuse. Oral Dis., 4: 4-8, 1998.
44. Bergler, W., Bier, H., and Ganzer, U. The expression of epidermal growth factor receptors in the oral mucosa of patients with oral cancer. Arch. Oto-rhinolaryngol., 246: 121-125, 1989.
45. Werkmeister, R., Brandt, B., and Joos, U. The erbB oncogenes as prognostic markers on oral squamous cell carcinomas. Am. J. Surg., 772: 681-683, 1996.
46. Grandis, J. R., Melhem, M. F., Barnes, E. L., and Tweardy, D. J. Quantitative immunohistochemical analysis of transforming growth factor-α and epidermal growth factor receptor in patients with squamous cell carcinoma of the head and neck. Cancer (Phila.), 78: 1284-1292, 1996.
47. Shin, D. M., Voravud, N., Ro, J. Y., Lee, J. S., Hong, W. K., and Hittelman, W. N. Sequential increase in proliferating cell nuclear antigen expression in head and neck tumorigenesis, a potential biomarker. J. Natl. Cancer Inst., 12: 971-978, 1993.
48. Schwindt, A. E., Savino, T. M., Lanfranchi, H. E., Marschoff, E., Cabrini, R. L., and Itoiz, M. E. Nucleolar organizer regions in lining epithelium adjacent to squamous cell carcinoma of human oral mucosa. Cancer (Phila.), 73: 2674-2679, 1994.
49. Van Oijen, M. G. C. T., Gilsing, M. M. A., Rijksen, G., Hordijk, G. J., and Slootweg, P. J. Increased number of proliferating cells in oral epithelium from smokers and ex-smokers. Oral Oncol., 34: 297-303, 1998.
50. Kirsch, D. G., and Kastan, M. B. Tumor-suppressor p53: implications for tumor development and prognosis. J. Clin. Oncol., 16: 3158-3168, 1998.
51. Kropveld, A., Rozemuller, E. H., Leppers, F. G. J., Scheidel, K. C., de Weger, R. A., Koole, R., Hordijk, G. J., Slootweg, P. J., and Tilanus, M. G. J. Sequencing analysis of RNA and DNA of exons 1 through 11 shows p53 gene alterations to be present in almost 100% of the head and neck squamous cell cancers. Lab. Invest., 79: 347-353, 1999.
52. Erber, R., Conradt, C., Homann, N., Enders, C., Finckh, M., Dietz, A., Weidauer, H., and Bosch, F. X. TP53 DNA contact mutations are selectively asscciated with allelic loss and have a strong clinical impact in head and neck cancer. Oncogene, 16: 1671-1679, 1998.
53. Midgley, C. A., and Lane, D. P. p53 protein stability in tumour cells is not determined by mutation but is dependent on Mdm2 binding. Oncogene, 15: 1179-1189, 1997.
54. Save, V., Nylander, K., and Hall, P. A. Why is p53 protein stabilized in neoplasia? Some answers but many more questions. J. Pathol., 184: 348-350, 1993.
55. el-Naggar, A. K., Lai, S., Luna, M. A., Zhou, X. D., Weber, R. S., Goepfert, H., and Batsakis, J. G. Sequential p53 mutation analysis of the preinvasive and invasive head and neck squamous carcinoma. Int. J. Cancer, 64: 196-201, 1995.
56. Shin, D. M., Kim, J., Ro, J. Y., Hittelman, J., Roth, J. A., Hong, W. K., and Hittelman, W. N. Activation of p53 expression in premalignant lesions during head and neck tumorigenesis. Cancer Res., 54: 321-326, 1994.
57. Van Oijen, M. G. C. T., van de Craats, J. G., and Slootweg, P. J. p53 overexpression in oral mucosa in relation to smoking. J. Pathol., 187: 469-474, 1999.
58. Nees, M., Homann, N., Discher, H., Andl, T., Enders, C., Herold-Mende, C., Schuhmann, A., and Bosch, F. X. Expression of mutated p53 occurs in tumor-distant epithelia of head and neck cancer patients; a possible molecular basis for the development of multiple tumors. Cancer Res., 53: 4189-4196, 1993.
59. Lavieille, J. P., Brambilla, E., Riva-Lavieille, C., Reyt, E., Charachon, R., and Brambilla, C. Immunohistochemical detection of p53 protein in preneoplastic lesions and squamous cell carcinoma of the head and neck. Acta Otolaryngol., 115: 334-339, 1995.
60. Cruz, I. B., Snijders, P. J., Meijer, C. J., Braakhuis, B. J., Snow, G. B., Walboomers, J. M., and van der Waal, I. p53 expression above the basal cell layer in oral mucosa is an early event of malignant transformation and has predictive value for developing oral squamous cell carcinoma. J. Pathol., 184: 360-368, 1998.
61. Waridel, F., Estreicher, A., and Bron, L. Field cancerisation and polyclonal p53 mutation in the upper aero-digestive tract. Oncogene, 14: 163-169, 1997.
62. Colucci, S., El-Gehani, R., Flint, S., and Mothersill, C. p53 mutations and protein expression in primary cultures of normal oral mucosa in smokers and non-smokers. Oral Oncol., 33: 240-246, 1997.
63. Nakanishi, Y., Noguchi, M., Matsuno, Y., Saikawa, M., Mukai, K., Shimosato. Y., and Hirohashi, S. p53 expression in multicentric squamous cell carcinoma and surrounding squamous epithelium of the upper aerodigestive tract. Cancer (Phila.), 75: 1657-1662, 1995.
64. Ogden, G. R., Chisholm, D. M., Morris, A. M., and Stevenson, J. H. Overexpression of p53 in normal oral mucosa of oral cancer patients does not necessarily predict further malignant disease. J. Pathol., 182: 180-184, 1997.
65. Blandino, G., and Strano, S. BCL-2: the pendulum of the cell fate. J. Exp. Clin. Cancer Res., 16: 3-10, 1997.
66. Birchall, M. A., Schock, E., Harmon, B. V., and Gobé, G. Apoptosis, mitosis, PCNA, and bcl-2 in normal, leucoplakic and malignant epithelia of the human oral cavity: prospective. In Vivo study. Oral Oncol., 33: 419-425, 1997.
67. Salinas, A. E., and Wong, M. G. Glutathione S-transferases: a review. Curr. Med. Chem., 6: 279-309, 1999.
68. Warholm, M., Guthenberg, C., and Mannervik, B. Molecular and catalytic properties of glutathione transferase mu from human liver: an enzyme efficiently conjugating epoxides. Biochemistry, 22: 3610-3617, 1983.
69. Lafuente, A., Pujol, F., Carretero, P., Villa, J. P., and Cuchi, A. Human glutathione S-transferase μ (GST-μ) deficiency as a marker for the susceptibility to bladder and larynx cancer among smokers. Cancer Lett., 68: 49-54, 1993.
70. Zhang, L., Xiao, Y., and Priddy, R. Increase in placental glutathione S-transferase in human oral epithelial dysplastic lesions and squamous cell carcinomas. J. Oral Pathol. Med., 23: 75-79, 1994.
71. Bongers, V., Snow, G. B., de Vries, N., Cattan, A. R., Hall, A. G., van der Waal, I., and Braakhuis, B. J. Second primary head and neck squamous cell carcinoma predicted by the glutathione 5-transferase expression in healthy tissue in the direct vicinity of the first tumor. Lab. Invest., 73: 503-510, 1995.
72. Sonenberg, N., and Gingras, A. C. The mRNA 5′ cap-binding protein eIF4E and control of cell growth. Curr. Opin. Cell. Biol., 10: 268-275, 1998.
73. Franklin, S., Pho, T., Abreo, F. W., Nassar, R., De Benedetti, A., Stucker, F. J., and Nathan, C. A. Detection of the proto-oncogene eIF4E in larynx and hypopharynx cancers. Arch. Otolaryngol. Head Neck Surg., 125: 177-182, 1999.
74. Tonks, N. K., and Charbonneau, H. Protein tyrosine phosphorylation and signal transduction. Trends Biochem. Sci., 14: 497-500, 1989.
75. Verschuur, H. P., Rijksen, G., van Oirschot, B. A., Schipper-Kester, G. P., Slootweg, P. J., Staal, G. E., and Hordijk, G. J. Protein tyrosine (de-)phosphorylation in head and neck squamous cell carcinoma. Eur. Arch. Oto-rhinolaryngol., 251: 12-16, 1994.
76. Weinberg, W. C., Howard, J. C., and Iannaconne, P. M. Histological demonstration of mosaicism in a series of chimeric rats produced between congenic strains. Science (Washington DC), 227: 524-527, 1985.
77. Wengler, G. S., Allen, R. C., Parolini, O., Smith. H., and Conley, M. E. Non-random X-chromosome inactivation in natural killer cells from obligate carriers of X-linked severe combined immunodeficiency. J. Immunol., 150: 700-704, 1993.
78. Worsham, M. J., Wolman, S. R., Carey, T. E., Zarbo, R. J., Benninger, M. S., and Van Dyke, D. L. Common clonal origin of synchronous primary head and neck squamous cell carcinomas: analysis by tumor karyotypes and fluorescence in situ hybridization. Human Pathol., 26: 251-261, 1995.
79. Scholes, A. G., Woolgar, J. A., Boyle, M. A., Brown, J. S., Vaughan, E. D., Hart, C. A., Jones, A. S., and Field, J. K. Synchronous oral carcinomas: independent or common clonal origin. Cancer Res., 58: 2003-2006, 1998.
80. van Oijen, M. G. C. T., Leppers van der Straat, F. G. J., Tilanus, M. G. J., and Slootweg, P. J. The origin of multiple squamous cell carcinomas in the aerodigestive tract. Cancer (Phila.), 88: 884-893, 2000.
81. Lydiatt, W. M., Anderson, P. E., Bazzana, T., Casale, M., Hughes, C. J., Huvos, A. G., Lydiatt, D. D., and Schantz, S. P. Molecular support for field cancerization in the head and neck. Cancer (Phila.), 82: 1376-1380, 1998.
82. Roz, L., Wu, C. L., Porter, S., Scully, C., Speight, P., Read, A., Sloan, P., and Thakker, N. Allelic imbalance on chromosome 3p in oral dysplastic lesions: an early event in oral carcinogenesis. Cancer Res., 56: 1228-1231, 1996.
83. Zhang, L., Michelsen, C., Cheng, X., Zeng, T., Priddy, R., and Rosin, M. P. Molecular analysis of oral lichen planus. A premalignant lesion? Am. J. Pathol., 151: 323-327, 1997.
84. Mao, L., Lee, J. S., Fan, Y. H., Ro, J. Y., Batsakis, J. G., Lippman, S., Hittelman, W., and Hong, W. K. Frequent microsatellite alterations at chromosomes 9p21 and 3p14b in oral premalignant lesions and their value in cancer risk assessment. Nat. Med., 2; 682-685, 1996.
85. Sun, P. C., El-Mofty, S. K., Haughy, B. H., and Scholnick, S. B. Allelic loss in squamous cell carcinomas of the larynx: discordance between primary and metastatic tumors. Genes Chromosomes Cancer (Phila.), 14: 145-148, 1995.
86. Ribeiro, U., Safatle-Ribeiro, A. V., Posner, M. C., Rosendale, B., Bakker, A., Swalsky, P. A., Kim, R., Reynolds, J. C., and Finkelstein, S. D. Comparative p53 mutational analysis of multiple primary cancers of the upper aerodigestive tract. Surgery (St. Louis), 120: 45-53, 1996.
87. Tjebbes, G. W. A., Leppers van der Straat, F. G. J., Tilanus, M. G. J., Hordijk, G. J., and Slootweg, P. J. p53 tumor suppressor gene as clonal marker in head and neck squamous cell carcinoma: p53 mutations in primary tumor and matched lymph node metastases. Oral Oncol., 35: 384-389, 1999.
88. El-Naggar, A. K., Hurr, K., Huff, V., Clayman, G. L., Luna, M. A., and Batsakis, J. G. Microsatellite instability in preinvasive and invasive head and neck squamous carcinoma. Am. J. Pathol., 148: 2067-2072, 1996.
89. Chung, K. Y., Mukhopadhyay, T., Kim, J., Casson, A., Ro, J. Y., Goepfert, H., Hong, W. K., and Roth, J. A. Discordant p53 gene mutations in primary head and neck cancers and corresponding second primary cancers of the upper aerodigestive tract. Cancer Res., 53: 1676-1683, 1993.
90. Califano, J., Leong, P. L., Koch, W. M., Eisenberger, C. F., Sidransky, D., and Westra, W. H. Second esophageal tumors in patients with head and neck squamous cell carcinoma: an assessment of clonal relationships. Clin. Cancer Res., 5: 1862-1867, 1999.
91. Javaherian, A., Vaccariello, M., Fusenig, N. E., and Garlick, J. A. Normal keratinocytes suppress early stages of neoplastic progression in stratified epithelium. Cancer Res., 58: 2200-2208, 1998.
92. Franklin, W. A., Gazdar, A. F., Haney, J., Wistuba, I. I., La Rosa, F. G., Kennedy, T., Ritchey, D. M., and Miller, Y. E. Widely dispersed p53 mutation in respiratory epithelium. J. Clin. Invest., 100: 2133-2137, 1997.
93. Batsakis, Y. G. Surgical excision margins: a pathologist's perspective. Adv. Anat. Pathol., 3: 140-148, 1999.
94. Brandwein, M., and Zhang, D. Y. Molecular margins. Arch. Otolaryngol., Head Neck Surg., 124: 841-842, 1998.
95. Brennan, J. A., Mao, L., Hruban, R. H., Boyle, J. O., Eby, Y. J., Koch, W. M., Goodman, S. N., and Sidransky, D. Molecular assessment of histopathological staging in squamous-cell carcinoma of the head and neck. N. Engl. J. Med., 332: 429-435, 1995.
96. Cloos, J., Spitz, M. R., Schantz, S. P., Hsu, T. C., Zhang, Z. F., Tobi, H., Braakhuis, B. J., and Snow, G. B. Genetic susceptibility to head and neck squamous cell carcinoma. J. Natl. Cancer Inst., 88: 530-534, 1996.