Occurrence of field cancerization in clinically normal oral mucosa: A systematic review and meta-analysis

Mamani, Mariela Peralta; Terrero-Pérez, Ángel; Tucunduva, Rosana Mara Adami; Rubira, Cássia Maria Fischer; Santos, Paulo Sérgio da Silva; Honório, Heitor Marques; Rubira-Bullen, Izabel Regina Fischer

doi:10.1016/j.archoralbio.2022.105544

Cited by 14 publications

(7 citation statements)

References 40 publications

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“…However, as demonstrated in both AKs and cSCCs, in chronic photodamaged areas p53 is often mutated, driving premature cell cycle progression and aberrant proliferation of cells before DNA damage has been repaired [ 28 ]. For this reason, p53 and Ki67, markers of cell proliferation, could be considered as indicators of field cancerization [ 29 , 30 ]. We therefore investigated whether the expression of normal p53 and Ki67 were altered in the CFC skin samples ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

Ex Vivo Analysis of Cell Differentiation, Oxidative Stress, Inflammation, and DNA Damage on Cutaneous Field Cancerization

Camillo,

Zavattaro,

Veronese

et al. 2024

IJMS

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Cutaneous field cancerization (CFC) refers to a skin region containing mutated cells’ clones, predominantly arising from chronic exposure to ultraviolet radiation (UVR), which exhibits an elevated risk of developing precancerous and neoplastic lesions. Despite extensive research, many molecular aspects of CFC still need to be better understood. In this study, we conducted ex vivo assessment of cell differentiation, oxidative stress, inflammation, and DNA damage in CFC samples. We collected perilesional skin from 41 patients with skin cancer and non-photoexposed skin from 25 healthy control individuals. These biopsies were either paraffin-embedded for indirect immunofluorescence and immunohistochemistry stain or processed for proteins and mRNA extraction from the epidermidis. Our findings indicate a downregulation of p53 expression and an upregulation of Ki67 and p16 in CFC tissues. Additionally, there were alterations in keratinocyte differentiation markers, disrupted cell differentiation, increased expression of iNOS and proinflammatory cytokines IL-6 and IL-8, along with evidence of oxidative DNA damage. Collectively, our results suggest that despite its outwardly normal appearance, CFC tissue shows early signs of DNA damage, an active inflammatory state, oxidative stress, abnormal cell proliferation and differentiation.

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Section: Resultsmentioning

confidence: 99%

Ex Vivo Analysis of Cell Differentiation, Oxidative Stress, Inflammation, and DNA Damage on Cutaneous Field Cancerization

Camillo,

Zavattaro,

Veronese

et al. 2024

IJMS

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“…However, combining data from two cohorts was not feasible due to technical limitations and differences in the sample collection. Moreover, it is well established that the area surrounding a tumor, even if microscopically normal, often harbors molecular alterations due to field cancerization extending beyond the visible margin [ 19 , 54 ]. Using such tissue as a control can lead to underestimating the differences between normal and tumor samples.…”

Section: Discussionmentioning

confidence: 99%

“…The potential of DNA methylation patterns as biomarkers for distinguishing cancer cells from their normal cell counterparts presents exciting opportunities for tailored diagnostic and therapeutic approaches [ 17 , 18 ]. Molecular analyses can offer potential advantages over cell morphology for detecting alterations in normal adjacent tissues (NAT) [ 19 ]. Notably, specific molecular changes might be more sensitive than readily discernible cellular morphological changes, potentially enabling the detection of precancerous or early-stage lesions missed by light microscopy [ 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

HOXA1 3′UTR Methylation Is a Potential Prognostic Biomarker in Oral Squamous cell Carcinoma

Sorroche,

Miranda,

Beltrami

et al. 2024

Cancers

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Background: HOXA1 is a prognostic marker and a potential predictive biomarker for radioresistance in head and neck tumors. Its overexpression has been associated with promoter methylation and a worse prognosis in oral squamous cell carcinoma (OSCC) patients. However, opposite outcomes are also described. The effect of the methylation of this gene on different gene regions, other than the promoter, remains uncertain. We investigated the methylation profile at different genomic regions of HOXA1 in OSCC and correlated differentially methylated CpG sites with clinicopathological data. Methods: The HOXA1 DNA methylation status was evaluated by analyzing data from The Cancer Genome Atlas and three Gene Expression Omnibus datasets. Significant differentially methylated CpG sites were considered with a |∆β| ≥ 0.10 and a Bonferroni-corrected p-value < 0.01. Differentially methylated CpGs were validated by pyrosequencing using two independent cohorts of 15 and 47 OSCC patients, respectively. Results: Compared to normal tissues, we found significantly higher DNA methylation levels in the 3′UTR region of HOXA1 in OSCC. Higher methylation levels in tumor samples were positively correlated with smoking habits and patients’ overall survival. Conclusions: Our findings suggest that HOXA1 gene body methylation is a promising prognostic biomarker for OSCC with potential clinical applications in patient monitoring.

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“…DNA aneuploidy 29 and chromosome aberrations30 are commonly used to detect field cancerization at the DNA level. Several markers (p53, Ki-67, 31 cytokeratin fragments 21-1, 28 variations in nucleolar organizer regions, 32 phosphatases and tensin homolog deleted on chromosome 10 allelic loss, 33 DEK overexpression, 34 micro RNA [hsa-miR-221, hsa-miR-21, hsa-miR-135b, and hsa-miR-29c] detection, 35 ATP-binding cassette subfamily G member 2, 36 MutL protein homolog 1, methylguanine-methyltransferase methylation, 37 interferonstimulated gene 15, 38 aldehyde dehydrogenase, Notch1, 39 and Bmi1 40 ) have been identified in pre-cancerization transformation into oral cancer, stimulating the cell cycle and promoting DNA replication (Figure 3).…”

Section: Markers Of Field Cancerizationmentioning

confidence: 99%

Oral field cancerization: Genetic profiling for a prevention strategy for oral potentially malignant disorders

et al. 2023

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Background: Oral cancer therapy, such as radiation or surgical treatment, has pernicious long-term effects that patients suffer throughout their life, the disability being considerable with delayed diagnosis. It is well known that many oral cancers develop from oral potentially malignant disorders (OPMDs). Patients diagnosed with OPMDs may have an increased risk of developing cancer anywhere in the oral cavity. Early detection and intervention could be essential prevention strategies to inhibit oral cancer progression. OPMDs may not immediately develop into carcinoma. However, this condition provides a “field” of specific abnormalities wherein evolving altered genetic cells can be explained with the “field cancerization” concept. Purpose: This review aims to describe the “field cancerization” concept in oral cancer and OPMD, which is expected to contribute to a better clinical management strategy for oral cancer prevention. Review: “Oral field cancerization” describes oral cancers that develop in multifocal areas of pre-cancerous changes. It can be found as histologically abnormal tissue surrounding the tumor, suggesting that oral cancer often consists of multiple independent lesions. Conclusion: The oral field cancerization concept should prompt healthcare professionals to remind their patients that frequent oral examination with histological studies and molecular testing is mandatory for those at high risk of developing malignancies.

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Occurrence of field cancerization in clinically normal oral mucosa: A systematic review and meta-analysis

Cited by 14 publications

References 40 publications

Ex Vivo Analysis of Cell Differentiation, Oxidative Stress, Inflammation, and DNA Damage on Cutaneous Field Cancerization

Ex Vivo Analysis of Cell Differentiation, Oxidative Stress, Inflammation, and DNA Damage on Cutaneous Field Cancerization

HOXA1 3′UTR Methylation Is a Potential Prognostic Biomarker in Oral Squamous cell Carcinoma

Oral field cancerization: Genetic profiling for a prevention strategy for oral potentially malignant disorders

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