Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications (original) (raw)
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British Journal of Cancer, 1998
Patients affected by squamous cell carcinoma of the head and neck (HNSCC) show frequent occurrence of multiple cancers and widespread precancerous lesions in the mucosa of the upper respiratory tract, a phenomenon known as field cancenzation. In this study, we investigated the role of genetic instability in the development of HNSCC and in particular in tumour multiplicity phenomena of the upper respiratory tract. For this purpose, we analysed microsatellite instability (Ml) and loss of heterozygosity (LOH) at 20 loci mapping on five chromosomal arms in 67 HNSCC patients, 45 of whom had a single cancer and 22 had multiple primary tumours. The possible involvement of the hMLH1 gene in genetic instability and as a potential target of 3p21 deletion phenomena in head and neck cancers was also investigated. Our data indicate that mismatch repair-related genetic instability plays a minor role in the carcinogenesis of HNSCC and in tumour multiplicity of the head and neck region. Moreover. our results exclude a role for the hMLH1 gene as a determinant of Ml and as a specific gene target of deletion at 3p21 in HNSCC. We conclude that presumably other genetic mechanisms. such as those hypothesized for Ml-negative hereditary non-polyposis colorectal cancer patients, may play a major role in the carcinogenesis of the mucosa of the upper respiratory tract. Keywords: head and neck; head and neck squamous cell carcinoma; microsatellite instability; field cancerization; tumour muftiplicity
Genetic Analysis of Head and Neck Squamous Cell Carcinoma and Surrounding Mucosa
Archives of Otolaryngology–Head & Neck Surgery, 1999
Comparative genomic hybridization was performed on head and neck squamous cell carcinoma and surrounding mucosa to determine whether common chromosomal aberrations could be detected that would predispose an individual to developing a second primary tumor. Design: Biopsy specimens were taken from 19 patients with squamous cell carcinoma of the head and neck, 3 samples from each person: 1 specimen from the tumor site and 1 each from 1 and 5 cm from the macroscopic tumor margin. Samples were snap frozen in liquid nitrogen. A portion of each distant sample and tissue taken from immediately adjacent to the site of the tumor specimen were sectioned and stained with hematoxylineosin, either to search by light microscopy for tumor cells or signs of dysplasia in the distant samples, or to determine whether the tumor specimen had substantial nontumor cell content. Tissue adjacent to the tumor biopsy site was used because the biopsy specimens were relatively small. Comparative genomic hybridization was performed on all samples. Subjects: Nineteen patients with newly diagnosed carcinomas of the head and neck. Results: The tumor biopsy specimens showed no substantial nontumor cell content, and the distant specimens were all histologically normal. The tumors showed multiple mutations: mean (SD) number of deletions, 5.4 (4.3); amplifications, 5.2 (4.6). Deletion of chromosome 3p was seen in 13 of 19 cases and was associated with amplification of 3q in 10 cases. No mutations were seen in the distant biopsy specimens. Conclusions: Frequently occurring chromosomal aberrations were seen in the tumor cells, suggesting a key role for these mutations in tumor development. Screening histologically normal upper aerodigestive tract mucosa with comparative genomic hybridization does not provide information on early genetic events that predispose a patient to developing a second primary tumor.
Genetic alterations in head and neck squamous cell carcinomas
Brazilian Journal of Medical and Biological Research, 1999
The genetic alterations observed in head and neck cancer are mainly due to oncogene activation (gain of function mutations) and tumor suppressor gene inactivation (loss of function mutations), leading to deregulation of cell proliferation and death. These genetic alterations include gene amplification and overexpression of oncogenes such as myc, erbB-2, EGFR and cyclinD1 and mutations, deletions and hypermethylation leading to p16 and TP53 tumor suppressor gene inactivation. In addition, loss of heterozygosity in several chromosomal regions is frequently observed, suggesting that other tumor suppressor genes not yet identified could be involved in the tumorigenic process of head and neck cancers. The exact temporal sequence of the genetic alterations during head and neck squamous cell carcinoma (HNSCC) development and progression has not yet been defined and their diagnostic or prognostic significance is controversial. Advances in the understanding of the molecular basis of head and neck cancer should help in the identification of new markers that could be used for the diagnosis, prognosis and treatment of the disease.
International Journal of Cancer, 2001
Patients affected by squamous cell carcinoma of the head and neck (HNSCC) show frequent occurrence of multiple cancers and widespread precancerous lesions in the mucosa of the upper respiratory tract, a phenomenon known as field cancenzation. In this study, we investigated the role of genetic instability in the development of HNSCC and in particular in tumour multiplicity phenomena of the upper respiratory tract. For this purpose, we analysed microsatellite instability (Ml) and loss of heterozygosity (LOH) at 20 loci mapping on five chromosomal arms in 67 HNSCC patients, 45 of whom had a single cancer and 22 had multiple primary tumours. The possible involvement of the hMLH1 gene in genetic instability and as a potential target of 3p21 deletion phenomena in head and neck cancers was also investigated. Our data indicate that mismatch repair-related genetic instability plays a minor role in the carcinogenesis of HNSCC and in tumour multiplicity of the head and neck region. Moreover. our results exclude a role for the hMLH1 gene as a determinant of Ml and as a specific gene target of deletion at 3p21 in HNSCC. We conclude that presumably other genetic mechanisms. such as those hypothesized for Ml-negative hereditary non-polyposis colorectal cancer patients, may play a major role in the carcinogenesis of the mucosa of the upper respiratory tract. Keywords: head and neck; head and neck squamous cell carcinoma; microsatellite instability; field cancerization; tumour muftiplicity
Head and neck squamous cell carcinoma (HNSCC) is a frequent malignancy with a poor survival rate. Identifying the tumor suppressor gene (TSG) loci by genomic studies is an important step to uncover the molecular mechanisms involved in HNSCC pathogenesis. Therefore, comprehensive analyses were performed to 170 subjects. They were 41 premalignat patients, 79 malignant patients, and 50 control subjects. The chromosomal aberrations included Translocation which ranged from 4.8% and 19% in premalignant and malignant HNSCCs, respectively. Gain ranged from 19.5% to 52%. While loss was found to be higher 29.3 and 87 in both. Duplication and breakpoint ranged 19.5% to 59.5% and 24.3% to 35.4% for premalignant and HNSCC, respectively. Loss of heterozygosity (LOH) and microsatellite instability (MSI) were detected and showed an allelic imbalance mainly in six regions (3pter-3p24.2, 5q33.3-q34, 9p21, 9q21.1-22.3, 17p, and 17p12) of chromosomes 3, 5, 9 and 17 in premalignant, and HNSCC patients c...
The role of genetic susceptibility in head and neck squamous cell carcinoma
2008
Our research is an additional genetic study to uncover the molecular mechanisms involved in head and neck squamous cell carcinoma (HNSCC) pathogenesis by studying loss of heterozygosity (LOH) and microsatellite instability (MSI) in both premalignant and malignant patients and to highlight the genotype of HNSCC in Upper Egypt. Patients with HNSCC from various parts of the world may have unique genotypes and this is the first genetic study of HNSCC in Sohag 500 KM to the south of Cairo. We performed a prospective study of 41 patients with precancerous and 79 patients with cancerous laryngeal, esophageal, nasopharyngeal, nasal and oral lesions, and 50 controls (The control patients were cases admitted for ear surgery or simple nasal surgery, from whom we took biopsy from mucosal lining of nasopharynx). The present study included 170 individuals who were admitted to the Ear, Nose and Throat department, Sohag University Hospital, Sohag, in Egypt in the period between April 2001 and March 2003. Samples which were taken by punch biopsy were frozen and stored at −80°C and were subjected to histopathological examination. We investigated LOH and MSI by using six microsatellite markers located at chromosomes 3, 5, 9, and 17. The markers used were D3S1286, D9S171, D9S753, D17S654, D17S695, and CFS1-R. LOH was in all premalignant and malignant lesions at 5q33.3-q34 and 13% of Controls. LOH at 17p21 was absent in all premalignant lesions and was found in 53% of malignant lesions and 12.4% of Controls. In premalignant lesions, LOH was at 3pter-3p24.2 (73% of cases), at 9p21 (46%), at 9q21.1-22.3 (37%), and at 17p13 (37%). These percents increased in malignant lesions to 87, 80, 67, and 63%, respectively. They were 14, 19.4, 17, and 19% in controls. Examination of LOH could improve diagnosis, adds additional confidence, in HNSCC by DNA extraction from suspicious lesions in high-risk groups (smokers and alcoholics) and LOH at 3p/9p seems to be of particular value for early detection and definition of progression risk. If there are high percent of LOH at these chromosomes, active intervention should be done (chemoprevention and regular follow up head and neck examination for very early detection and management).
A hereditary motion model of the cell carinoma of the skin and neck is not yet clarified, and the aero digestive plot is also obscuring the inherited cause for field cancerization. 87 head and neck injuries, including pre-injury and coronary sores associated with the presentation of cancer-causing chemicals, have been tested using the 10 main chromosomal chromosome alellic microsatellite disease studies characterized in previous years. In every histopathological enterprise of childhood hyperplasia, the continuum from chromosomal disorders to in situ carcinoma to invasive malignant growth is fair. Our current research was conducted at Mayo Hospital, Lahore from May 2019 to April 2020. Adjacent tissue territories with a different histopathological appearance have regularly changed the hereditary influence, as well as that of more advanced histopathological ally areas, which has demonstrated extra hereditary modifications and irregular mucosal cells which involve widespread and micro-invasive sores have imparted fundamental hereditary modifications to these lessons. Based on these results, the scientific marvel in the neighborhood of field cancer seems to require the production and relocation of clonally associated paraneoplastic cells.
Genetic profile of head and neck squamous cell carcinoma: clinical implications
The Journal of Laryngology & Otology, 2008
The outcome for patients with head and neck squamous cell carcinoma remains poor, despite improvements in diagnosis and treatment over the past three decades. This has triggered great interest in the genetic events that underpin the aetiology and clinical behaviour of this group of cancers. As a result, the genetic profile for head and neck squamous cell carcinomas at different sub-sites has been relatively well characterised at the chromosomal level. Various studies have shown links between specific aberrations in head and neck squamous cell carcinoma and clinical outcome, e.g. loss of heterozygosity at 2q and 18q is commonly associated with poor prognosis, and loss of heterozygosity at 9p21 is associated with recurrence. However, there is as yet no significant clinical application of this genetic knowledge as regards the screening, diagnosis or treatment of head and neck squamous cell carcinoma. Here, we summarise the current state of knowledge, and highlight the most promising ar...