Allelic imbalance at chromosomal loci implicated in the pathogenesis of oral precancer, cumulative loss and its relationship with progression to cancer

Partridge, M; Emilion, G; Pateromichelakis, S.; A’Hern, Roger; Phillips, Elaine; Langdon, John H.

doi:10.1016/s1368-8375(97)00052-3

Cited by 84 publications

(56 citation statements)

References 12 publications

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“…The identification of molecular genetic activity detects lesions that may become malignant. This facilitates the clinical intervention and prevents surgical injuries (16). The expression of p53 may be associated with the development of OSCC and dysplasia, being more evident in the early stages of carcinogenesis (17) due to the lack of apoptosis and the continuous Table I.…”

Section: Discussionmentioning

confidence: 99%

Retinoblastoma and p53 protein expression in pre-malignant oral lesions and oral squamous cell carcinoma

et al. 2012

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Abstract. The retinoblastoma (Rb) and p53 genes play a fundamental role in cell cycle mechanisms, and their deregulation is related to many steps of oral cancer carcinogenesis. This study was conducted to evaluate the expression of the p53 and Rb proteins in malignant and pre-malignant oral cavity lesions. This retrospective study was conducted at the Federal University of Bahia, Salvador, Brazil, and the Molecular Biology Laboratory of the Otorhinolaryngology Department at the University of Heidelberg, Heidelberg, Germany. Excisional biopsy samples of oral cavities were collected from patients with suspected oral lesions. The samples were processed by immunohistochemistry to be classified by a semi-quantitative score: samples with a ≤10% positivity were considered to have weak/negative expression (-); those with 11-50% positivity, moderate expression (+); and those with >50% positivity, high expression (++). Seventy-one patients were studied (75% male; median age, 52 years; range, 24-84). Of the samples studied, 59.4% were oral squamous cell carcinoma (OSCC) and 40.6% were pre-neoplastic lesions (leukoplakia and actinic cheilitis). OSCC presented higher expression of Rb protein compared to pre-malignant lesions: 75 vs. 25% (p<0.001). Pre-neoplastic lesions presented higher expression of p53 protein compared to OSCC lesions: 55.2 vs. 44.8% (p= 0.030). Despite the small number of samples, the expression of these cell cycle biomarkers (p53 and Rb protein) in excisional biopsies suggests that molecular lesion assessment can determine pre-malignant lesions, and that its use may improve the clinical and surgical treatment of early lesions. Thus, p53 protein expression may be related to the early steps of carcinogenesis in OSCC. Finally, a higher Rb expression was also observed in malignant lesions.

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Section: Discussionmentioning

confidence: 99%

Retinoblastoma and p53 protein expression in pre-malignant oral lesions and oral squamous cell carcinoma

et al. 2012

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“…19 Arguments against this vision arise from studies showing high MSI incidences in pre-malignant lesions and in young patients. 20,24 Most studies report on a lack of MMR gene defects in HNSCC compared with HNPCC. 14,21,24,29 This could either indicate a low incidence of MSI or a higher proportion of non-MMR MSI cases.…”

Section: What Are Msi and Loh?mentioning

confidence: 99%

The clinical relevance of microsatellite alterations in head and neck squamous cell carcinoma: a critical review

Schutter¹,

Spaepen²,

Bride

et al. 2007

Eur J Hum Genet

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Triggered by the existing confusion in the field, the current paper aimed to review the current knowledge of both microsatellite instability (MSI) and loss of heterozygosity (LOH) detected by microsatellite markers in head and neck squamous cell carcinoma (HNSCC), and to provide the reader with an assessment of their prognostic and predictive value in this tumor type. For both MSI and LOH, various detection methods were included such as mono-and polynucleotidemarkers and gel-as well as automated analyses. Only studies based on PCR techniques with microsatellite markers were considered. Taking the methodological problems occurring in investigations with microsatellite markers into account, LOH seems to be more common than MSI in HNSCC. Although both types of microsatellite alterations have been correlated with clinicopathological features of this tumor type, only LOH seems to have a clear prognostic value. The predictive value of both MSI and LOH is debatable. More research has to be performed to clearly establish LOH detection as a translational application in the HNSCC field, aiming to predict response to treatments or outcome, and eventually to use as a therapeutic target.

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“…Loss of heterozygosity (LOH) studies using microsatellite markers on head-and-neck malignancies have demonstrated extensive areas of loss. [1][2][3][4][5] Moreover, premalignant lesions studied in the initial description of a genetic progression model revealed the timing of genetic alterations such as LOH as premalignant lesions advance toward malignancy. 6 These specific genetic events can be detected in the saliva and serum of patients with head and neck malignancy, 7,8 opening the door to new strategies for early cancer detection and tumor surveillance.…”

mentioning

confidence: 99%

Progression of microsatellite instability from premalignant lesions to tumors of the head and neck

Pilkington

Westra

et al. 2002

Intl Journal of Cancer

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The role of microsatellite alterations other than loss of heterozygosity (LOH) in the progression of benign epithelium to head-and-neck squamous cell cancer (HNSCC) has not been previously described. As the severity of the dysplasia increases at the microscopic level, there is an increase in the prevalence of LOH as defined by microsatellite analysis. Other alterations have been detected in the form of microsatellite instability (MSI), represented by insertions or deletions of base pairs. It is unknown, however, whether the prevalence of these alterations likewise increases during these early stages of tumor progression. Key words: microsatellite instability; head-and-neck squamous cell carcinoma; loss of heterozygosity; hereditary nonpolyposis colon cancerThe molecular progression of head-and-neck squamous cell carcinoma (HNSCC) correlates with the phenotypic spectrum of dysplasia found in premalignant lesions of the upper respiratory tract epithelium. Loss of heterozygosity (LOH) studies using microsatellite markers on head-and-neck malignancies have demonstrated extensive areas of loss. [1][2][3][4][5] Moreover, premalignant lesions studied in the initial description of a genetic progression model revealed the timing of genetic alterations such as LOH as premalignant lesions advance toward malignancy. 6 These specific genetic events can be detected in the saliva and serum of patients with head and neck malignancy, 7,8 opening the door to new strategies for early cancer detection and tumor surveillance. These genetic alterations included LOH and other microsatellite changes, such as simple insertions or deletions of base pairs, referred to as microsatellite instability (MSI).These simple base pair insertions/deletions are dominant features of certain solid tumors with significant mismatch repair (MMR) defects, such as hereditary non-polyposis colon cancer (HNPCC). 9 However, the reduced prevalence of such alterations and the lack of mutations in gene products known to maintain MMR functions in HNSCC do not support classification of HNSCC as a tumor type with a dominant feature of MMR deficiency. Nevertheless, when detected in HNSCC at selected loci, the shifted alleles can be quite useful in detecting the presence of altered clonal populations in body fluids, including saliva and serum. 7,8 It is important to emphasize that the microsatellite markers selected in these studies were known to exhibit LOH and MSI in lung tumors; therefore, identification of MSI in these head-andneck tumors does not implicate HNSCC as an MMR-deficient tumor type.However, MSI has not been studied comprehensively in premalignant lesions of the head and neck. Further definition of the temporal occurrence of such alterations in premalignant lesions in HNSCC should provide insight into the detection of premalignant lesions using analyses of both MSI and LOH.We looked at 5 different categories of head-and-neck lesions, predominantly from the oral cavity: hyperplasia without atypia, mild dysplasia, moderate dysplasia, severe dysplasia/ca...

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Allelic imbalance at chromosomal loci implicated in the pathogenesis of oral precancer, cumulative loss and its relationship with progression to cancer

Cited by 84 publications

References 12 publications

Retinoblastoma and p53 protein expression in pre-malignant oral lesions and oral squamous cell carcinoma

Retinoblastoma and p53 protein expression in pre-malignant oral lesions and oral squamous cell carcinoma

The clinical relevance of microsatellite alterations in head and neck squamous cell carcinoma: a critical review

Progression of microsatellite instability from premalignant lesions to tumors of the head and neck

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