Expression of p63 and CD44 in oral squamous cell carcinoma and correlation with clinicopathological parameters

Saghravanian, Nasrollah; Anvari, Kazem; Ghazi, Narges; Memar, Bahram; Shahsavari, Maryam; Aghaee, Monavar Afzal

doi:10.1016/j.archoralbio.2017.06.011

Cited by 28 publications

(19 citation statements)

References 23 publications

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“…Our results are partly in agreement with Saghravanian et al who showed significantly high p63 expression in association with tumor stage and LN metastases in oral SCCs [90, 91]. In the current study, we demonstrated that a higher p63 (intense) expression was significantly associated with poor OS; it should be emphasized that the prognostic value of p63 expression is still controversial [90, 92-94]. This lack of consensus may be attributed to testing different p63 isoforms with different biologic properties and the small number of cases that were included in these studies.…”

Section: Discussionsupporting

confidence: 94%

“…Yet, the current findings are in agreements with the reported association of p63 expression and SCC differentiation in experimental animal models, head and neck squamous cell cancer, oral SCC, nasopharyngeal cancer, lung cancer, and epidermal tumor [83-89]. Our results are partly in agreement with Saghravanian et al who showed significantly high p63 expression in association with tumor stage and LN metastases in oral SCCs [90, 91]. In the current study, we demonstrated that a higher p63 (intense) expression was significantly associated with poor OS; it should be emphasized that the prognostic value of p63 expression is still controversial [90, 92-94].…”

Section: Discussionsupporting

confidence: 93%

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Prognostic Role of Epithelial-Mesenchymal Transition Markers “E-Cadherin, β-Catenin, ZEB1, ZEB2 and p63” in Bladder Carcinoma

2019

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BackgroundThis study aimed to investigate the expression of epithelial-mesenchymal markers’ E-cadherin, β-catenin, zinc-finger E-box-binding homeobox 1 (ZEB1), zinc-finger E-box-binding homeobox 2 (ZEB2) and p63 in transitional cell carcinoma (TCC) and squamous cell carcinoma (SCC) variants of bladder carcinoma (BC) and their correlation with clinicopathological parameters of prognostic importance.MethodsIn this retrospective study, 91 patients were enrolled (66 with TCC and 25 with SCC). All patients had full clinical and follow-up data and available paraffin blocks. Immunohistochemical analysis was performed and correlated with clinicopathological factors.ResultsIn TCC cases, reduced E-cadherin, β-catenin positivity and p63 expression rate were evident in the sitting of increased expression of ZEB1 and ZEB2. Patients with ZEB2 positive tumors were more likely to die compared to those with negative ZEB2 (P = 0.024). Moreover, in patients with muscle-invasive BCs, an intense p63 expression was associated with poor overall survival (OS) (P < 0.001). For patients with SCC, there was a reduction in E-cadherin and β-catenin positivity with elevated p63 expression and concomitant increased ZEB1 and ZEB2 expression. Poor prognosis was evident in association with reduced E-cadherin, positive nuclear β-catenin/reduced membranous β-catenin, ZEB1 and ZEB2 positive cases as well patients with elevated p63 expression (P < 0.001). TCC and SCC cases showed similar poor prognosis in association with elevated p63 expression (P < 0.001).ConclusionsIn both TCC and SCC variants, epithelial-mesenchymal transition (EMT) process is evident; however, its molecular mechanism shows some variations, specifically this notably different p63 expression pattern among two carcinoma variants with the similar impact of elevated p63 expression pattern on prognosis.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 93%

Prognostic Role of Epithelial-Mesenchymal Transition Markers “E-Cadherin, β-Catenin, ZEB1, ZEB2 and p63” in Bladder Carcinoma

2019

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“…In upper vertebrates, the ZEB family includes two proteins, ZEB1 and ZEB2, which act as either transcriptional repressors or activators depending on the target gene and tissue. 60 [74][75][76][77][78] Indeed, altered ΔNp63 expression is also present in oral epithelial dysplasia, playing a potential role in malignant transformation of epithelial cells. 79,80 4.5 | Additional transcription factors E12 and E47, encoded by the E2A gene, belong to the same transcription factor family of Twist proteins.…”

Section: Zeb Familymentioning

confidence: 99%

Epithelial‐to‐mesenchymal transition in oral squamous cell carcinoma: Challenges and opportunities

Ling

Cheng

Tao

2020

Intl Journal of Cancer

134

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Oral squamous cell carcinoma (OSCC) is the most common malignancy representing 90% of all forms of oral cancer worldwide. Although great efforts have been made in the past decades, the 5‐year survival rate of OSCC patients is no more than 60% due to tumor metastasis and subsequent recurrence. The metastasis from the primary site is due to a complex process known as epithelial‐to‐mesenchymal transition (EMT). During the EMT, epithelial cells gradually acquire the structural and functional characteristics of mesenchymal cells, leading to the upregulation of cell migration and the promotion of tumor cell dissemination. Therefore, EMT attracted broad attention due to its close relationship with cancer invasion and metastasis. Therefore, in the present review, an extensive description of the current research on OSCC and the role of EMT in this cancer type is provided, including diverse EMT markers, regulatory networks and crucial EMT‐inducing transcription factors in OSCC. Moreover, a brief summary was made regarding the current application of EMT‐correlated indexes in the prognostic analysis of OSCC patients, and the potential therapeutic approaches against OSCC and difficulties in the development of an effective anti‐EMT treatment are discussed. Our aim is to provide novel insights to develop new strategies to combat OSCC by targeting EMT.

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“…Defining these specific cancer stem cell (CSC) populations has remained controversial and identifying markers for these resistant CSC populations presents a goal toward developing targeted therapies. Multiple CSC markers have been proposed for squamous cell carcinomas, including the cell surface markers CD44, CD133, and “stem cell” signaling proteins SOX2, MYC, and p63 [113,114,115,116]. Ripamonti et al [117] demonstrated that treatment of SCC cell lines with epithelial growth factor led to an increase in ΔNp63α expression and tumor initiating cell proliferation, indicating the importance of ΔNp63α in SCC tumor stem cell maintenance [117].…”

Section: Dysregulated δNp63α Disrupts An Extensive Network Of Molementioning

confidence: 99%

Molecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis

Moses

George

Sakakibara

et al. 2019

IJMS

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The p63 gene is a member of the p53/p63/p73 family of transcription factors and plays a critical role in development and homeostasis of squamous epithelium. p63 is transcribed as multiple isoforms; ΔNp63α, the predominant p63 isoform in stratified squamous epithelium, is localized to the basal cells and is overexpressed in squamous cell cancers of multiple organ sites, including skin, head and neck, and lung. Further, p63 is considered a stem cell marker, and within the epidermis, ΔNp63α directs lineage commitment. ΔNp63α has been implicated in numerous processes of skin biology that impact normal epidermal homeostasis and can contribute to squamous cancer pathogenesis by supporting proliferation and survival with roles in blocking terminal differentiation, apoptosis, and senescence, and influencing adhesion and migration. ΔNp63α overexpression may also influence the tissue microenvironment through remodeling of the extracellular matrix and vasculature, as well as by enhancing cytokine and chemokine secretion to recruit pro-inflammatory infiltrate. This review focuses on the role of ΔNp63α in normal epidermal biology and how dysregulation can contribute to cutaneous squamous cancer development, drawing from knowledge also gained by squamous cancers from other organ sites that share p63 overexpression as a defining feature.

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Expression of p63 and CD44 in oral squamous cell carcinoma and correlation with clinicopathological parameters

Cited by 28 publications

References 23 publications

Prognostic Role of Epithelial-Mesenchymal Transition Markers “E-Cadherin, β-Catenin, ZEB1, ZEB2 and p63” in Bladder Carcinoma

Prognostic Role of Epithelial-Mesenchymal Transition Markers “E-Cadherin, β-Catenin, ZEB1, ZEB2 and p63” in Bladder Carcinoma

Epithelial‐to‐mesenchymal transition in oral squamous cell carcinoma: Challenges and opportunities

Molecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis

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