PL EN


Preferences help
enabled [disable] Abstract
Number of results
2016 | 63 | 3 | 505-509
Article title

Expression profiles of MGMT, p16, and APC genes in tumor and matching surgical margin from patients with oral squamous cell carcinoma

Content
Title variants
Languages of publication
EN
Abstracts
EN
The aim of the study was to assess the expression of MGMT, p16, and APC genes in tumors and matching surgical margin samples from 56 patients with primary OSCC. We also analyzed the association of the clinical variables with the expression of the studied genes. After RNA isolation and cDNA synthesis gene expression levels were assessed by quantitative reverse transcription (qRT)-PCR. Two-sided parametrical Student's t-test for independent groups with equal/unequal variances showed no statistically significant differences in genes' expression in tumor compared to margin samples. No association was found between the genes' expression and clinical parameters, except for MGMT, whose low expression was probably associated with smoking (0.87 vs 1.34, p=0.065). 'Field cancerization' is an area with genetically or epigenetically altered cells and at the same time a risk factor for cancer. Disturbances in gene expression could also be the source of damages leading to cancerization. In conclusion, it is important to mention that the field remaining after a surgery may pose an increased risk of cancer development. It may be suggested that the diagnosis and treatment of cancers should not be concentrated only on the tumor itself, but also on the cancer field effect. Therefore, further molecular analysis on surgical margins and additional research regarding their assessment are required.
Keywords
Publisher

Year
Volume
63
Issue
3
Pages
505-509
Physical description
Dates
published
2016
received
2015-10-20
revised
2016-03-04
accepted
2016-05-18
(unknown)
2016-08-05
Contributors
  • Department of Medical and Molecular Biology, School of Medicine with the Division of Dentistry, Medical University of Silesia in Zabrze, Katowice, Poland
  • Department of Medical and Molecular Biology, School of Medicine with the Division of Dentistry, Medical University of Silesia in Zabrze, Katowice, Poland
  • Clinic of Oncological and Reconstructive Surgery, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland
  • Department of Statistics, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland
References
  • Ai L, Stephenson KK, Ling W, Zuo C, Mukunyadzi P, Suen JY, Hanna E, Fan CY (2003) The p16 (CDKN2a/INK4a) tumor-suppressor gene in head and neck squamous cell carcinoma: a promoter methylation and protein expression study in 100 cases. Mod Pathol 16: 944-50.
  • Angadi PV, Savitha JK, Rao SS, Sivaranjini Y (2012) Oral field cancerization: current evidence and future perspectives. Oral Maxillofac Surg 16: 171-180. doi: 10.1007/s10006-012-0317-x.
  • Argiris A, Brockstein BE, Haraf DJ (2004) Competing causes of death and second primary tumors in patients with locoregionally advanced head and neck cancer treated with chemoradiotherapy. Clin Cancer Res 10: 1956-1962.
  • Bagan JV, Scully C (2008) Recent advances in Oral Oncology 2007: epidemiology, aetiopathogenesis, diagnosis and prognostication. Oral Oncol 44: 103-108.
  • Braakhuis BJ, Tabor MP, Kummer JA, Leemans CR, Brakenhoff RH (2003) A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications. Cancer Res 63: 1727-1730.
  • Braakhuis BJ, Bloemena E, Leemans CR, Brakenhoff RH (2010) Molecular analysis of surgical margins in head and neck cancer: more than a marginal issue. Oral Oncol 46: 485-491. doi: 10.1016/j.oraloncology.2010.01.019.
  • Chen YJ, Rau KM, Chien CY, Fang FM, Huang TL, Chiu TJ (2011) High p16 expression predicts a positive response to chemoradiotherapy in stage IVa/b head and neck squamous cell carcinoma. Asian Pac J Cancer Prev 12: 649-655.
  • Christmann M, Kaina B (2012) O(6)-methylguanine-DNA methyltransferase (MGMT): impact on cancer risk in response to tobacco smoke. Mutat Res 736: 64-74. doi: 10.1016/j.mrfmmm.2011.06.004.
  • Cordeiro AT, Silva CM, Bartchewsky Júnior W, Ribeiro ML, Martinez CA (2012) Evaluation of the expression of the MGMT gene in normal and neoplastic tissue of patients with colorectal cancer. Rev Col Bras Cir 39: 48-53.
  • Demokan S, Dalay N (2011) Role of DNA methylation in head and neck cancer. Clin Epigenetics 2: 123-150. doi: 10.1007/s13148-011-0045-3.
  • Elango KJ, Suresh A, Erode EM, Subhadradevi L, Ravindran HK, Iyer SK, Iyer SK, Kuriakose MA (2011) Role of human papilloma virus in oral tongue squamous cell carcinoma. Asian Pac J Cancer Prev 12: 889-896.
  • El-Naggar AK, Kim HW, Clayman GL, Coombes MM, Le B, Lai S, Zhan F, Luna MA, Hong WK, Lee JJ (2002) Differential expression profiling of head and neck squamous carcinoma: significance in their phenotypic and biological classification. Oncogene 21: 8206-8219.
  • Gollin SM (2014) Cytogenetic alterations and their molecular genetic correlates in head and neck squamous cell carcinoma: a next generation window to the biology of disease. Genes Chromosomes Cancer 53: 972-990. doi: 10.1002/gcc.22214.
  • Guha N, Boffetta P, Wünsch Filho V, Eluf Neto J, Shangina O, Zaridze D, Curado MP, Koifman S, Matos E, Menezes A, Szeszenia-Dabrowska N, Fernandez L, Mates D, Daudt AW, Lissowska J, Dikshit R, Brennan P (2007) Oral health and risk of squamous cell carcinoma of the head and neck and esophagus: results of two multicentric case-control studies. Am J Epidemiol 166: 1159-1173.
  • Hashibe M, Brennan P, Chuang SC, Boccia S, Castellsague X, Chen C, Curado MP, Dal Maso L, Daudt AW, Fabianova E, Fernandez L, Wünsch-Filho V, Franceschi S, Hayes RB, Herrero R, Kelsey K, Koifman S, La Vecchia C, Lazarus P, Levi F, Lence JJ, Mates D, Matos E, Menezes A, McClean MD, Muscat J, Eluf-Neto J, Olshan AF, Purdue M, Rudnai P, Schwartz SM, Smith E, Sturgis EM, Szeszenia-Dabrowska N, Talamini R, Wei Q, Winn DM, Shangina O, Pilarska A, Zhang ZF, Ferro G, Berthiller J, Boffetta P (2009) Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomarkers Prev 18: 541-550. doi: 10.1158/1055-9965.EPI-08-0347.
  • Huber GF, Albinger-Hegyi A, Soltermann A, Roessle M, Graf N, Haerle SK, Holzmann D, Moch H, Hegyi I (2011) Expression patterns of Bmi-1 and p16 significantly correlate with overall, disease-specific, and recurrence-free survival in oropharyngeal squamous cell carcinoma. Cancer 117: 4659-4670. doi: 10.1002/cncr.26100.
  • Jacob R, Shafiei N, Nagel G, Welkoborsky HJ, Mann W, Kaina B (2010) MGMT activity in mucosal epithelium and squamous cell carcinoma of the head and neck. Anticancer Res 30: 2561-2566.
  • Kang HS, Roh JL, Kim MJ, Cho KJ, Lee SW, Kim SB, Choi SH, Nam SY, Kim SY (2016) Predictive factors for long-term survival in head and neck squamous cell carcinoma patients with distant metastasis after initial definitive treatment. J Cancer Res Clin Oncol 142: 295-304. doi: 10.1007/s00432-015-2043-x.
  • Kordi-Tamandani DM, Moazeni-Roodi AK, Rigi-Ladiz MA, Hashemi M, Birjandian E, Torkamanzehi A (2010) Promoter hypermethylation and expression profile of MGMT and CDH1 genes in oral cavity cancer. Arch Oral Biol 55: 809-814. doi: 10.1016/j.archoralbio.2010.06.017.
  • Lee KH, Lee JS, Nam JH, Choi C, Lee MC, Park CS, Juhng SW, Lee JH (2011) Promoter methylation status of hMLH1, hMSH2, and MGMT genes in colorectal cancer associated with adenoma-carcinoma sequence. Langenbecks Arch Surg 396: 1017-1026. doi: 10.1007/s00423-011-0812-9.
  • Majchrzak E, Szybiak B, Wegner A, Pienkowski P, Pazdrowski J, Luczewski L, Sowka M, Golusinski P, Malicki J, Golusinski W (2014) Oral cavity and oropharyngeal squamous cell carcinoma in young adults: a review of the literature. Radiol Oncol 48: 1-10. doi: 10.2478/raon-2013-0057.
  • Marini A, Mirmohammadsadegh A, Nambiar S, Gustrau A, Ruzicka T, Hengge UR (2006) Epigenetic inactivation of tumor suppressor genes in serum of patients with cutaneous melanoma. J Invest Dermatol 126: 422-431.
  • McCormack A, Kaplan W, Gill AJ, Little N, Cook R, Robinson B, Clifton-Bligh R (2013) MGMT expression and pituitary tumours: relationship to tumour biology. Pituitary 16: 208-219. doi: 10.1007/s11102-012-0406-8.
  • Miracca EC, Kowalski LP, Nagai MA (1999) High prevalence of p16 genetic alterations in head and neck tumours. Br J Cancer 81: 677-83.
  • Ohta S, Uemura H, Matsui Y, Ishiguro H, Fujinami K, Kondo K, Miyamoto H, Yazawa T, Danenberg K, Danenberg PV, Tohnai I, Kubota Y (2009) Alterations of p16 and p14ARF genes and their 9p21 locus in oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 107: 81-91. doi: 10.1016/j.tripleo.2008.08.027.
  • Perez-Ordoñez B, Beauchemin M, Jordan RC (2006) Molecular biology of squamous cell carcinoma of the head and neck. J Clin Pathol 59: 445-453.
  • Pérez-Sayáns M, Suárez-Peñaranda JM, Herranz-Carnero M, Gayoso-Diz P, Barros-Angueira F, Gándara-Rey JM, García-García A (2012) The role of the adenomatous polyposis coli (APC) in oral squamous cell carcinoma. Oral Oncol 48: 56-60. doi: 10.1016/j.oraloncology.2011.09.001.
  • Reed AL, Califano J, Cairns P, Westra WH, Jones RM, Koch W, Ahrendt S, Eby Y, Sewell D, Nawroz H, Bartek J, Sidransky D (1996) High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma. Cancer Res 56: 3630-3633.
  • Risk MC, Knudsen BS, Coleman I, Dumpit RF, Kristal AR, LeMeur N, Gentleman RC, True LD, Nelson PS, Lin DW (2010) Differential gene expression in benign prostate epithelium of men with and without prostate cancer: evidence for a prostate cancer field effect. Clin Cancer Res 16: 5414-5423. doi: 10.1158/1078-0432.CCR-10-0272.
  • Robbins KT, Ferlito A, Shah JP, Hamoir M, Takes RP, Strojan P, Khafif A, Silver CE, Rinaldo A, Medina JE (2013) The evolving role of selective neck dissection for head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol 270: 1195-1202. doi: 10.1007/s00405-012-2153-x.
  • Rodríguez MJ, Acha A, Ruesga MT, Rodríguez C, Rivera JM, Aguirre JM (2007) Loss of expression of DNA repair enzyme MGMT in oral leukoplakia and early oral squamous cell carcinoma. A prognostic tool? Cancer Lett 245: 263-268.
  • Sailasree R, Abhilash A, Sathyan KM, Nalinakumari KR, Thomas S, Kannan S (2008) Differential roles of p16INK4A and p14ARF genes in prognosis of oral carcinoma. Cancer Epidemiol Biomarkers Prev 17: 414-420. doi: 10.1158/1055-9965.EPI-07-0284.
  • Schena M, Guarrera S, Buffoni L, Salvadori A, Voglino F, Allione A, Pecorari G, Ruffini E, Garzino-Demo P, Bustreo S, Consito L, Bironzo P, Matullo G (2012) DNA repair gene expression level in peripheral blood and tumour tissue from non-small cell lung cancer and head and neck squamous cell cancer patients. DNA Repair (Amst) 11: 374-380. doi: 10.1016/j.dnarep.2012.01.003.
  • Schmitz S, Machiels JP, Weynand B, Gregoire V, Hamoir M (2009) Results of selective neck dissection in the primary management of head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol 266: 437-443. doi: 10.1007/s00405-008-0767-9.
  • Shah JP (1990) Patterns of cervical lymph node metastasis from squamous carcinomas of the upper aerodigestive tract. Am J Surg 160: 405-409.
  • Shen L, Kondo Y, Rosner GL, Xiao L, Hernandez NS, Vilaythong J, Houlihan PS, Krouse RS, Prasad AR, Einspahr JG, Buckmeier J, Alberts DS, Hamilton SR, Issa JP (2005) MGMT promoter methylation and field defect in sporadic colorectal cancer. J Natl Cancer Inst 97: 1330-1338.
  • Slaughter DP, Southwick HW, Smejkal W (1953) Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 6: 963-968.
  • Szukała K, Brieger J, Bruch K, Biczysko W, Wierzbicka M, Szyfter W, Szyfter K (2004) Loss of heterozygosity on chromosome arm 13q in larynx cancer patients: analysis of tumor, margin and clinically unchanged mucosa. Med Sci Monit 10: CR233-40.
  • Uesugi H, Uzawa K, Kawasaki K, Shimada K, Moriya T, Tada A, Shiiba M, Tanzawa H (2005) Status of reduced expression and hypermethylation of the APC tumor suppressor gene in human oral squamous cell carcinoma. Int J Mol Med 15: 597-602.
  • Ushijima T (2007) Epigenetic field for cancerization. J Biochem Mol Biol 40: 142-150.
  • Vigneswaran N, Williams MD (2014) Epidemiologic trends in head and neck cancer and aids in diagnosis. Oral Maxillofac Surg Clin North Am 26: 123-141. doi: 10.1016/j.coms.2014.01.001.
  • Worsham MJ, Chen KM, Meduri V, Nygren AO, Errami A, Schouten JP, Benninger MS (2006) Epigenetic events of disease progression in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 132: 668-677.
  • Yakushiji T, Noma H, Shibahara T, Arai K, Yamamoto N, Tanaka C, Uzawa K, Tanzawa H (2001) Analysis of a role for p16/CDKN2 expression and methylation patterns in human oral squamous cell carcinoma. Bull Tokyo Dent Coll 42: 159-168.
Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv63p505kz
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.