Characterization of stem‐like cancer cells in basal cell carcinoma and its surgical margins

Milošević, Maja; Lazarević, Miloš; Toljic, Bosko; Simonović, Jelena; Trišić, Dijana; Nikolic, Nadja; Petrović, Milan; Milašin, Jelena

doi:10.1111/exd.13755

Cited by 15 publications

(18 citation statements)

References 31 publications

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“…This finding could help explaining, not only the recurrence of certain tumors after complete resection, but also the presence of genetic changes in seemingly normal tissue, like in some of our cases. 30 However, the exact significance of this finding in the specific context of our study is not possible to determine with our available data. Considering all these genomic alterations identified in both group of samples, we verified that gain in 3p and 16p, and loss in 14q and 20p show potential to discriminate sBCC samples from rtBCC samples Our results seem to indicate that particularly 3p12.3, 3p14.2, 14q22.2 and 16p13.11 display potential to distinguish with statistical significance BCC samples accordingly to the risk factors in its origin, suggesting that genes in these chromosome bands may have a important role in BCC carcinogenesis.…”

Section: Discussionmentioning

confidence: 68%

Basal cell carcinomas of the scalp after radiotherapy for tinea capitis in childhood: A genetic and epigenetic study with comparison with basal cell carcinomas evolving in chronically sun‐exposed areas

Cardoso

Ribeiro

Caramelo

et al. 2021

Experimental Dermatology

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Background: Basal cell carcinoma (BCC) has been mostly associated with sun exposure, but ionizing radiation is also a known risk factor. It is not clear if the pathogenesis of BCC, namely at a genomic and epigenetic level, differs according to the underlying triggering factors.Objective: The present study aims to compare genetic and epigenetic changes in BCCs related to ionizing radiation and chronic sun exposure. Methods:Tumor samples from BCCs of the scalp in patients submitted to radiotherapy to treat tinea capitis in childhood and BCCs from sun-exposed areas were analysed through array comparative genomic hybridization (array-CGH) and methylationspecific multiplex ligation-dependent probe amplification (MS-MLPA) to detect copy number alterations and methylation status of specific genes.Results: Genomic characterization of tumor samples revealed several copy number gains and losses in all chromosomes, with the most frequent gains observed at 2p, 6p, 12p, 14q, 15q, 18q, Xp and Yp, and the most frequent losses observed at 3q, 14q, 16p, 17q, 22q, Xp, Yp and Yq. We developed a statistical model, encompassing gains in 3p and 16p and losses in 14q and 20p, with potential to discriminate BCC samples with sporadic aetiology from BCC samples that evolve after radiotherapy in childhood for the treatment of tinea capitis, which presented statistical significance (P = 0.003).Few methylated genes were detected through MS-MLPA, most frequently RARB and CD44.Conclusions: Our study represents a step forward in the understanding of the genetic mechanisms underlying the pathogenesis of BCC and suggests potential differences according to the underlying ris k factors.

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Section: Discussionmentioning

confidence: 68%

Basal cell carcinomas of the scalp after radiotherapy for tinea capitis in childhood: A genetic and epigenetic study with comparison with basal cell carcinomas evolving in chronically sun‐exposed areas

Cardoso

Ribeiro

Caramelo

et al. 2021

Experimental Dermatology

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“…Despite the low mortality rates and the rare occurrence of metastasis, basal cell carcinoma may be locally invasive and relapse after treatment, causing significant morbidity. This could be due to the existence of cancers stem cells in surgical margins of BCCs, as suggested by Milosevic et al [ 3 ]. Local tissue destruction and disfigurement can be considerable if not limited by early detection and treatment.…”

Section: Introductionmentioning

confidence: 94%

Loss of EphA7 Expression in Basal Cell Carcinoma by Hypermethylation of CpG Islands in the Promoter Region

Liu

Xiao

et al. 2022

Analytical Cellular Pathology

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Basal cell carcinoma (BCC) is the most common malignancy worldwide, with increasing incidence. BCCs present low mortality but high morbidity, and its pathogenesis remains unclear. Eph receptors have been implicated in tumorigenesis. EphA7 plays a role as a tumor suppressor in certain cancers. We checked EphA7 expression levels and methylation status in a set of BCCs, benign skin diseases, and compound nevus tissue samples using immunohistochemistry. EphA7 protein was positively expressed in normal basal cells, benign skin diseases, and compound nevus cells, but lost in areas of BCC tissues. We detected hypermethylation in BCC tissue samples with reduced expression of EphA7. There is a significant relationship between the expression level of EphA7 receptor protein and the methylation status of CpG islands in the EphA7 promoter region ( P < 0.001 ). To our knowledge, this is the first study to report the EphA7 expression profile and hypermethylation of EphA7 in BCC. The role of the EphA7 gene and the status of hypermethylation in tumorigenesis and treatment of BCC warrant further investigation.

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“… 27 , 30 , 31 , 35 , 36 Recent evidence indicates that CSCs within surgical margins play a crucial role in the clinical outcomes of cancer. 37 – 39 Lazarevic et al 38 showed that the surgical margins of oral cancer express stem cell markers, such as CD44, Oct-4, CD133, Nanog and SOX2, which have the ability to form spheroids to become resistant to chemotherapy. CSCs survive and promote cancer, as they maintain low levels of reactive oxygen species (ROS) levels and exhibit redox patterns matching those of normal stem cells.…”

Section: Alterations In the Expression Pattern Of Om-scms In Osf Opmmentioning

confidence: 99%

Loss of oral mucosal stem cell markers in oral submucous fibrosis and their reactivation in malignant transformation

Sharma¹,

Fonseca

Hunter

et al. 2020

Int J Oral Sci

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The integrity of the basal stem cell layer is critical for epithelial homoeostasis. In this paper, we review the expression of oral mucosal stem cell markers (OM-SCMs) in oral submucous fibrosis (OSF), oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) to understand the role of basal cells in potentiating cancer stem cell behaviour in OSF. While the loss of basal cell clonogenicity triggers epithelial atrophy in OSF, the transition of the epithelium from atrophic to hyperplastic and eventually neoplastic involves the reactivation of basal stemness. The vacillating expression patterns of OM-SCMs confirm the role of keratins 5, 14, 19, CD44, β1-integrin, p63, sex-determining region Y box (SOX2), octamer-binding transcription factor 4 (Oct-4), c-MYC, B-cell-specific Moloney murine leukaemia virus integration site 1 (Bmi-1) and aldehyde dehydrogenase 1 (ALDH1) in OSF, OPMDs and OSCC. The downregulation of OM-SCMs in the atrophic epithelium of OSF and their upregulation during malignant transformation are illustrated with relevant literature in this review.

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Characterization of stem‐like cancer cells in basal cell carcinoma and its surgical margins

Abstract: Basal cell carcinomas expressed stem cell markers, pointing to the existence of a cancer cell side population with stemness characteristics. Margin also appeared to harbour a small number of cancer-initiating cells.

Cited by 15 publications

References 31 publications

Basal cell carcinomas of the scalp after radiotherapy for tinea capitis in childhood: A genetic and epigenetic study with comparison with basal cell carcinomas evolving in chronically sun‐exposed areas

Basal cell carcinomas of the scalp after radiotherapy for tinea capitis in childhood: A genetic and epigenetic study with comparison with basal cell carcinomas evolving in chronically sun‐exposed areas

Loss of EphA7 Expression in Basal Cell Carcinoma by Hypermethylation of CpG Islands in the Promoter Region

Loss of oral mucosal stem cell markers in oral submucous fibrosis and their reactivation in malignant transformation

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