Table 1.
A summary of the most important studies on the role of microsatellite instability (MSI) and MMR dysfunction in the progression of head and neck cancer (HNC) precancerous lesions. ACC, adenoid cystic carcinoma; CIS, carcinoma in situ; SCC, squamous cell carcinoma.
| Authors | Year | Lesion | Site | Methods | Main Results |
|---|---|---|---|---|---|
| Wang et al. [38] | 2001 | SCC | Oral cavity | Methylation-sensitive enzyme + PCR amplification + Immunohistochemistry (hMSH2, hMLH1) | No correlation between hMLH1/hMSH2 genes inactivation and MSI development |
| Ohki et al. [39] | 2001 | Pleomorphic adenomas, salivary carcinomas | Salivary glands | PCR amplification + Immunohistochemistry (hMSH2) | No significant expression difference between benign and malignant tumors |
| Ha K et al. [40] | 2002 | Dysplasia, CIS, SCC | Oral cavity | PCR amplification | Increasing amount of MSI rate as histologic grade increases in severity |
| Castrilli et al. [41] | 2002 | Pleomorphic adenomas, Warthin’s tumors, malignant tumors | Salivary glands | Immunohistochemistry (hMSH2, hMLH1) |
Benign neoplasms expressed lower levels of both hMSH2 and hMLH1 proteins compared to malignant tumors |
| Pimenta FJ et al. [42] | 2004 | Lichen planus | Oral cavity | Immunohistochemistry (hMSH2) |
Reduced expression of hMSH2 in oral lichen planus elevates the risk of OSCCs |
| Sardi I et al. [43] | 2006 | Preinvasive lesions, invasive cancers | Larynx | PCR amplification | MSI+ preinvasive lesions are at higher risk of evolving in invasive cancers |
| Demokan S et al. [44] | 2006 | SCC, adenoma, ACC, Warthin tumor, sarcoma | Larynx, Salivary glands, Oral cavity, nasal/paranasal sinus, and nasopharynx, glomus | Methylation-sensitive enzyme + PCR amplification | MSI significantly associated with HN cancers |
| Sanguansin S et al. [45] | 2006 | SCC | Oral cavity | PCR amplification | Polymorphism of hMSH2 can be used as a biomarker for prognosis and follow-up in OSCC treatment |
| Sengupta S et al. [46] | 2007 | Leukoplakia and SCC | Oral cavity and larynx | Methylation-sensitive enzyme + PCR amplification + Immunohistochemistry (hMSH2, hMLH1) | Promoter regions hypermethylation has a positive correlation with tobacco use |
| Czerninski R et al [47] | 2009 | SCC | Oral cavity | Immunohistochemistry (hMSH2, hMLH1) + PCR amplification | OSCC presented hypermethylation of hMSH2 and hMLH1 promoters |
| Tobón-Arroyave SI et al. [48] | 2009 | Pleomorphic adenoma | Minor salivary glands | Immunohistochemistry (hMSH2, hMLH1) |
Lower hMSH2/ hMLH1 expression correlated with a higher risk for malignant transformation |
| De Schutter H et al. [49] | 2009 | SCC | Generic H&N tumors | PCR amplification | MSI has a low prevalence in HNSCC |
| Yalniz Z et al. [50] | 2010 | SCC + unspecified other types | Larynx + unspecified other sites | PCR amplification | More than 1 every 4 HN cancer is positive for MSI |
| Ashazila MJJ et al. [51] | 2011 | SCC | Oral cavity | PCR amplification | MSI status significantly correlated with tumor stage and differentiation grade |
| Tawfik HM et al. [52] | 2011 | SCC | Generic H&N tumors | Immunohistochemistry (hMLH1) + methylation-specific PCR | 86.7% of the sample showed hMLH1 promoter hypermethylation |
| Caldeira PC et al. [53] | 2011 | Leukoplakia | Oral cavity | Immunohistochemistry (hMLH1) |
Lower expression in severe dysplasia |
| Caldeira PC et al. [54] | 2011 | Leukoplakia | Oral cavity | Immunohistochemistry (hMLH1) |
Lower expression in severe dysplasia |
| Souza LR et al. [55] | 2011 | Actinic cheilitis and LSCC | Lips | Immunohistochemistry (hMSH2) |
Premalignant and malignant lip disease exhibit changes in the expression of hMSH2 proteins |
| González-Ramírez et al. [56] | 2011 | SCC | Oral cavity | Immunohistochemistry (hMLH1) + methylation-specific PCR | hMLH1 promoter methylation seems to be related to early stage OSCC |
| Theocharis S et al. [57] | 2011 | SCC | Mobile tongue | Immunohistochemistry (hMSH2, hMLH1) |
Higher hMSH2 and MLH1 expression is significantly associated with a lower stage |
| Helal Tel A et al. [58] | 2012 | SCC | Oral cavity | Immunohistochemistry (hMSH2) |
Lower expression in OSCC |
| Sarmento DJS et al. [59] | 2013 | Actinic cheilitis and LSCC | Lips | Immunohistochemistry (hMSH2, hMLH1) |
Lower expression in OSCC |
| Jha R et al. [60] | 2013 | SCC | Oral cavity | PCR amplification (hMLH1) |
Polymorphism in this gene may be related to OSCC predisposition |
| Mondal P et al. [61] | 2013 | Leukoplakia and SCC | Oral cavity | PCR amplification | Polymorphism in hMSH3 may be related to OSCC predisposition |
| de Oliveira DH et al. [62] | 2014 | Actinic cheilitis | Lower lip | Immunohistochemistry (hMLH1) |
Lower expression in severe dysplasia |
| Nogueria GAS et al. [63] | 2015 | SCC | Oral cavity | PCR amplification | Polymorphism in the MMR system may be related to OSCC predisposition |
| Jessri M et al. [64] | 2015 | SCC | Oral cavity | Immunohistochemistry (hMSH2, hMSH6, hMLH1, PMS2) | Focal lack of hMSH6 indicates carcinoma in situ |
| Jessri M et al. [65] | 2015 | Leukoplakia and SCC | Oral cavity | Immunohistochemistry (hMSH2, hMSH6, hMLH1, PMS2) | Lower expression in severe dysplasia (except hMSH6) |
| Lopes ML et al. [66] | 2016 | Actinic cheilitis and LSCC | Lips | Immunohistochemistry (hMSH2) |
hMSH2 mutation seems to be related to early events in the cancerization process |
| Vasan K et al. [67] | 2019 | SCC | Oral cavity | Immunohistochemistry (hMSH2, hMSH6, hMLH1, PMS2) | MMR proteins loss in OSCC is associated with more advanced primary tumors |