Nachweis von TP53-Mutationen mittels Exfoliativzytologie (brush biopsy) oraler Leukoplakien

Scheifele, Christian; Schlechte, Horst; Bethke, Gudrun; Reichart, P. A.

doi:10.1007/s10006-002-0425-0

Cited by 14 publications

(4 citation statements)

References 18 publications

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“…Mutations in the p53 suppressor gene might be useful for the prognosis of oral cancer (51, 52). This methodological approach also needs clinical verification.…”

Section: Improved Analytical Methodsmentioning

confidence: 99%

“…Combined with liquid-based cytology, the visualization of malignant cells using antibodies against human cytokeratin AE1 and AE3 is possible, but its validity has not been actually proven (38). Mutations in the p53 suppressor gene might be useful for the prognosis of oral cancer (51,52). This methodological approach also needs clinical verification.…”

Section: Molecular Analysesmentioning

confidence: 99%

See 1 more Smart Citation

Oral cytology revisited

Mehrotra

Hüllmann

Smeets

et al. 2009

J Oral Pathology Medicine

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During the last decade, oral cytology has once again become the focus of scientific research. This new interest is due to the introduction of a cytobrush for cell collection as well as a computer-assisted analysis (Oral CDx). Although promising, the sensitivity and specificity of conventional oral brush cytology remains limited. To circumvent the problems and improve the accuracy, various adjunctive analytical methods have been attempted. DNA analysis, immunocytochemical and molecular analysis are suggested methodological cytology approaches to improve the validity of oral brush cytology. An increase in sensitivity (up to 100%) and specificity (up to 100%) of oral brush biopsy has been reported on localized pre-malignant and malignant lesions. Oral brush biopsy probably will not replace histopathology in the definitive diagnosis of oral cancer, but it might be valuable for the prevention of misdiagnosis of clinically doubtful oral lesions and for the monitoring of lesions that might proceed on to oral cancer.

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“…Mutations in the p53 suppressor gene might be useful for the prognosis of oral cancer (51, 52). This methodological approach also needs clinical verification.…”

Section: Improved Analytical Methodsmentioning

confidence: 99%

Section: Molecular Analysesmentioning

confidence: 99%

Oral cytology revisited

Mehrotra

Hüllmann

Smeets

et al. 2009

J Oral Pathology Medicine

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show abstract

“…Scheifele et al describe TP53 mutations as a prognostic parameter for malignant transformation in the mouth. 18 They analyzed the prevalence of mutations of the TP53 tumor suppressor gene (exons 5-8) by PCR and TGGE in patients with oral leukoplakia. The mutation frequency was 57.7% in patients with oral squamous carcinoma, approximately 39.5% with oral leukoplakia, and 0% in the healthy control group.…”

Section: Discussionmentioning

confidence: 99%

Clinical value of vesical leukoplakia and evaluation of the neoplastic risk by mutation analyses of the tumor suppressor gene TP53

Staack¹,

Schlechte²,

Sachs³

et al. 2006

Int J of Urology

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Aim: Leukoplakia has been found to be precancerous in organs covered with squamous epithelium. The present study was conducted to determine whether leukoplakia described in the female bladder is also a premalignant lesion. Methods: Between 1973 and 1996, 77 female patients were diagnosed with vesical leukoplakia by cystoscopy and cytology and were followed-up until 2004 (mean follow-up time: 8.3 years). A survey was conducted to analyze exposure to cocarcinogens. Additionally, DNA was isolated from 36 urine sediments and analyzed for TP53 mutations. The results were compared to the mutation frequency of TP53 in urine sediments from patients diagnosed with transitional cell carcinoma (TCC) of the bladder and healthy controls. Results: The whitish lesion was mostly located at the trigone and varied in size and location during the follow-up years. TP53 mutations were detected in 6 out of 36 urine samples in exons 5, 6 and 7 (mutation frequency: 16.7%). Among control patients with no leukoplakia or TCC of the bladder (n = 70), the spontaneous mutation frequency was similar (14.3%). In contrast, the mutation frequency in patients with TCC of the bladder (n = 148) revealed 39.9% in exons 5, 6, 7 and 8. The present study did not show any statistically significant correlations between chronic inflammations, TP53 mutations, exposure to carcinogens and vesical leukoplakia. Conclusions: Our data suggest that vesical leukoplakia does not necessarily hold neoplastic potential and needs to be clearly distinguished from leukoplakia in other localizations. Therefore, we suggest that a biopsy can be omitted, if follow-up controls by cystoscopy are performed regularly.

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“…Знание подобных вариантов позволило бы разработать ПЦР-и NGS-тест-системы для выявления клинически значимых генетических вариантов. Имеющиеся крайне немногочисленные исследования показывают, что в клетках некоторых лейкоплакий были выявлены патогенные мутации гена tp53; они особенно часто обнаруживались при диспластических процессах эпителия и у лиц, курящих и злоупотребляющих алкоголем [3,4]. Есть указания на то, что количество одновременно выявляемых при ЛСОРП мутаций гена tp53 напрямую связано со степенью эпителиальной дисплазии, ввиду чего подобные мутации являются ранними событиями канцерогенеза СОРП [5,6].…”

Section: Introductionunclassified

Clinical Significance of Pathogenicity of Somatic Mutations in Oral Leukoplakia: a Prospective Observational Study

Karpuk,

Rubnikovich,

Zhyltsov

et al. 2023

Kuban. nauсh. med. vestnik

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Background. The vast majority of malignant neoplasms of the oral mucosa refer to squamous cell carcinomas. The development of squamous cell carcinoma of the oral mucosa is often promoted by previous potentially malignant diseases, with oral leukoplakia dominating among them.Objective. To determine the clinical significance of the pathogenicity of somatic mutations in oral mucosal leukoplakia.Methods. The study material included 24 samples of abnormal epithelium of the oral mucosa from leukoplakia patients. QIAamp DNA FFPE Tissue Kit (Qiagen, Germany) was used for deoxyribonucleic acid (DNA) extraction from the samples. DNA sequencing was performed using IlluminaNextSeq 550 sequencer and TruSight™ Oncology 500 DNA Kit For Use with NextSeq (Illumina, USA). All DNA extractions from biological samples, preparation and sequencing of DNA libraries were performed step-by-step in strict accordance with the guidelines provided with the respective reagent kits. Bioinformatics analysis was carried out using specific software Illumina Base Space (Illumina, USA) and Galaxy Project (The Galaxy Community, a non-profit international project) according to current guidelines. The desired power of the study accounted for 90%. Two Proportions Z test was performed by means of The Sample Size Calculation of Statistica 12 (StatSoft, Inc.) with the set option “one-tailed hypothesis”, because it was initially assumed that pathogenic (oncogenic) genetic variants occur in the tissue of oral leukoplakia much more frequently than in the human reference genome used for sequence alignment.Results. The pathogenic somatic mutations in the TP53, KRAS, APC, NRAs and BRAF genes, identified in this study, alone or in combination, are highly likely (hazard ratio 3000-11000) to be associated with the development of oral mucosal leukoplakia and low-grade epithelial dysplasia. The multiplicity of pathogenic and likely pathogenic genetic variants associated with epithelial dysplasia, as well as the fact that a number of variants do not occur in all patients, suggests that the same histotype of oral mucosal dysplasia may develop under the influence of different mutations.Conclusion. The pathogenic and likely pathogenic variants of the TP53, KRAS, APC, NRAS and BRAF genes, identified in this study, alone or in combination, are highly likely (hazard ratio 3000–11000) to be associated with the development of leukoplakia and low-grade epithelial dysplasia.

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Nachweis von TP53-Mutationen mittels Exfoliativzytologie (brush biopsy) oraler Leukoplakien

Abstract: TP53 mutations could be a useful prognostic indicator in precancerous oral lesions. Although the brush biopsy technique appears simple clinically, further investigations are necessary to specify the implications of genetic analysis.

Cited by 14 publications

References 18 publications

Oral cytology revisited

Oral cytology revisited

Clinical value of vesical leukoplakia and evaluation of the neoplastic risk by mutation analyses of the tumor suppressor gene TP53

Clinical Significance of Pathogenicity of Somatic Mutations in Oral Leukoplakia: a Prospective Observational Study

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