Abstract
The aim of this study was to investigate the association between microsatellite alteration in the surgical margins and local recurrence of oral cavity squamous cell carcinoma patients. Surgical specimens confirmed by pathological examination and corresponding surgical margins were collected from 120 oral cavity squamous cell carcinoma patients. Ten microsatellite markers were examined in the tumor specimens and paired surgical margins, which proved to be negative on pathological assessment. The specimens and surgical margins were amplified by polymerase chain reaction followed by computerized analysis. Forty-two specimens (35.0 %) with microsatellite instability (MSI) in at least one marker were found, and more than half of the specimens (n = 73, 60.8 %) had loss of heterozygosity (LOH) in at least one marker. Although MSI and LOH were not associated with the prognosis of oral cavity squamous cell carcinoma patients, presence of MSI in the tumor-free surgical margins increased the risk of local recurrence (hazard ratio: 9.549; 95 % confidence interval: 4.143–22.01). Genetic analysis of tumor-free surgical margins is a useful tool for identifying oral cavity squamous cell carcinoma patients who are vulnerable to local recurrence.
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Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108
Simard EP, Torre LA, Jemal A (2014) International trends in head and neck cancer incidence rates: differences by country, sex and anatomic site. Oral Oncol 50:387–403
Hsu SH, Wong YK, Wang CP, Wang CC, Jiang RS, Chen FJ, Liu SA (2013) Survival analysis of patients with oral squamous cell carcinoma with simultaneous second primary tumors. Head Neck 35:1801–1807
Tsai WC, Kung PT, Wang ST, Huang KW, Liu SA (2015) Beneficial impact of multidisciplinary team management on the survival in different stages of oral cavity cancer patients: results of a nationwide cohort study in Taiwan. Oral Oncol 51:105–111
De Schutter H, Spaepen M, McBride WH, Nuyts S (2007) The clinical relevance of microsatellite alterations in head and neck squamous cell carcinoma: a critical review. Eur J Hum Genet 15:734–741
Watson MM, Berg M, Søreide K (2014) Prevalence and implications of elevated microsatellite alterations at selected tetranucleotides in cancer. Br J Cancer 111:823–827
Temam S, Casiraghi O, Lahaye JB, Bosq J, Zhou X, Julieron M, Mamelle G, Lee JJ, Mao L, Luboinski B, Benard J, Janot F (2004) Tetranucleotide microsatellite instability in surgical margins for prediction of local recurrence of head and neck squamous cell carcinoma. Clin Cancer Res 10:4022–4028
Popat S, Hubner R, Houlston RS (2005) Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol 23:609–618
Deganello A, Gitti G, Mannelli G, Meccariello G, Gallo O (2013) Risk factors for multiple malignancies in the head and neck. Otolaryngol Head Neck Surg 149:105–111
Ashazila MJ, Kannan TP, Venkatesh RN, Hoh BP (2011) Microsatellite instability and loss of heterozygosity in oral squamous cell carcinoma in Malaysian population. Oral Oncol 47:358–364
Lee SH, Lee NH, Jin SM, Rho YS, Jo SJ (2011) Loss of heterozygosity of tumor suppressor genes (p16, Rb, E-cadherin, p53) in hypopharynx squamous cell carcinoma. Otolaryngol Head Neck Surg 145:64–70
Murali A, Sailasree R, Sebastian P, Rejnish Kumar R, Varghese BT, Kannan S (2011) Loss of heterozygosity of D9S162: molecular predictor for treatment response in oral carcinoma. Oral Oncol 47:571–576
Mahale A, Saranath D (2000) Microsatellite alterations on chromosome 9 in chewing tobacco-induced oral squamous cell carcinomas from India. Oral Oncol 36:199–206
Koy S, Plaschke J, Luksch H, Friedrich K, Kuhlisch E, Eckelt U, Martinez R (2008) Microsatellite instability and loss of heterozygosity in squamous cell carcinoma of the head and neck. Head Neck 30:1105–1113
Arai K, Shibahara T, Yamamoto N, Noma H (2002) The presence of candidate tumor suppressor gene loci at chromosome 3p for oral squamous cell carcinomas. Oral Oncol 38:763–771
Partridge M, Pateromichelakis S, Phillips E, Emilion GG, A’Hern RP, Langdon JD (2000) A case-control study confirms that microsatellite assay can identify patients at risk of developing oral squamous cell carcinoma within a field of cancerization. Cancer Res 60:3893–3898
Brennan JA, Mao L, Hruban RH, Boyle JO, Eby YJ, Koch WM, Goodman SN, Sidransky D (1995) Molecular assessment of histopathological staging in squamous-cell carcinoma of the head and neck. N Engl J Med 332:429–435
Pena Murillo C, Huang X, Hills A, McGurk M, Lyons A, Jeannon JP, Odell E, Brown A, Lavery K, Barrett W, Sherriff M, Brakenhoff R, Partridge M (2012) The utility of molecular diagnostics to predict recurrence of head and neck carcinoma. Br J Cancer 107:1138–1143
Nathan CO, Franklin S, Abreo FW, Nassar R, De Benedetti A, Glass J (1999) Analysis of surgical margins with the molecular marker eIF4E: a prognostic factor in patients with head and neck cancer. J Clin Oncol 17:2909–2914
Mao L, Clark D (2015) Molecular margin of surgical resections-Where do we go from here? Cancer 121:1914–1916
Hayashi M, Wu G, Roh JL, Chang X, Li X, Ahn J, Goldsmith M, Khan Z, Bishop J, Zhang Z, Zhou XC, Richmon J, Agrawal N, Koch WM (2015) Correlation of gene methylation in surgical margin imprints with locoregional recurrence in head and neck squamous cell carcinoma. Cancer 121:1957–1965
Silver CE, Beitler JJ, Shaha AR, Rinaldo A, Ferlito A (2009) Current trends in initial management of laryngeal cancer: the declining use of open surgery. Eur Arch Otorhinolaryngol 266:1333–1352
Subramanian S, Mishra RK, Singh L (2003) Genome-wide analysis of microsatellite repeats in humans: their abundance and density in specific genomic regions. Genome Biol 4:R13
Tabor MP, Brakenhoff RH, van Houten VM, Kummer JA, Snel MH, Snijders PJ, Snow GB, Leemans CR, Braakhuis BJ (2001) Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications. Clin Cancer Res 7:1523–1532
Zienolddiny S, Aguelon AM, Mironov N, Mathew B, Thomas G, Sankaranarayanan R, Yamasaki H (2004) Genomic instability in oral squamous cell carcinoma: relationship to betel-quid chewing. Oral Oncol 40:298–303
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The authors thank the Biostatistics Task Force of Taichung Veterans General Hospital for assisting with the statistical analysis.
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The study was funded by the National Science Council, Taiwan, Republic of China (NSC 101-2314-B- 075A-005-MY3) and the Ministry of Health and Welfare, Taiwan, Republic of China (MOHW104-TDU-B-211-124-004).
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
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Lin, JC., Wang, CC., Jiang, RS. et al. Impact of microsatellite alteration in surgical margins on local recurrence in oral cavity cancer patients. Eur Arch Otorhinolaryngol 274, 431–439 (2017). https://doi.org/10.1007/s00405-016-4215-y
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DOI: https://doi.org/10.1007/s00405-016-4215-y