Cyclin D1, E‐cadherin and beta‐catenin expression in FIGO Stage IA cervical squamous carcinoma: diagnostic value and evidence for epithelial–mesenchymal transition

Koay, Mei Hui Eleanor; Crook, Maxine L.; Stewart, Colin J.R.

doi:10.1111/j.1365-2559.2012.04326.x

Cited by 30 publications

(24 citation statements)

References 37 publications

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“…Our results have demonstrated that the loss of β -catenin expression strongly characterises the transition from cells at the central tumour to invasive nests or isolated tumour cells in elderly patients with VSCC having no HPV infection (Table 7). Similar findings have been recorded in cervical squamous carcinoma, in which there was reduced β -catenin immunoexpression in many of infiltrative tumour cells, particularly at the tumour–stromal interface (Koay et al , 2012). In the present study, loss of β -catenin expression was statistically associated with FIGO stages III and IV, and Cox regression model also demonstrated that loss β -catenin expression was an independent factor associated with poor survival (Table 8).…”

Section: Discussionsupporting

confidence: 80%

Epithelial-mesenchymal transition-like events in vulvar cancer and its relation with HPV

et al. 2013

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Background:Epithelial-to-mesenchymal transition (EMT) still remains an obscure event in vulvar squamous cell carcinoma (VSCC).Methods:Immunohistochemistry (IHC) expression of E-cadherin, β-catenin, Snail, Slug, Twist and Vimentin was analysed in 87 VSCC, controlled for human papillomavirus (HPV) positivity, considering tumour front and central tumour as different morphological categories from the same tumour.Results:Lower β-catenin and higher Vimentin expression was associated with invasive front when compared with the central tumour (P=0.013 and P⩽0.001, respectively). Higher expression of E-cadherin in central tumour was significantly related to absence of vascular and perineural invasion, lower invasion depth and ⩽2 lymph node involvement. Loss of β-catenin and high Slug, Snail and Twist expression was associated with HPV-negative tumours. Moreover, β-catenin lower expression associated with gain in Slug expression predicts a subgroup with worst outcome (P=0.001). Lower expression of β-catenin in both central tumour and invasive front correlated with lower overall survival (P=0.021 and P=0.011, respectively). Also, multivariate analysis showed that lower β-catenin expression was independently associated with poorer outcome (P=0.044).Conclusion:Human papillomavirus-related tumours show better prognosis and outcome; besides, they do not progress through EMT phenomenon. Immunohistochemical analysis of β-catenin in invasive tumour front is a key issue for establishing prognosis of vulva cancer.

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Section: Discussionsupporting

confidence: 80%

Epithelial-mesenchymal transition-like events in vulvar cancer and its relation with HPV

et al. 2013

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“…They also showed gradual increase of cyclin D1 expression with progression from dysplasia to invasive cancers, which is agreement with our result. This slight increase of cyclin D1 in cervical cancer may be associated with the involvement of cyclin D1 in the acquisition of invasive potential [38]. Recent studies have revealed the specific function of cyclin D1 in cell migration [3940].…”

Section: Discussionmentioning

confidence: 99%

Glycogen synthase kinase 3β and cyclin D1 expression in cervical carcinogenesis

et al. 2016

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ObjectiveGlycogen synthase kinase 3β (GSK3β) is a pluripotent protein kinase involved in the development of cancers through regulation of numerous oncogenic molecules. Cyclin D1, an important regulator of G1 to S phase transition in various cells, is one of target proteins that GSK3β regulate. Our objective was to assess the expression of GSK3β and cyclin D1 in cervical neoplasm of different histologic grades and to identify their correlation in cervical carcinogenesis.MethodsImmunohistochemical analysis of GSK3β and cyclin D1 was performed in a total of 137 patients with 12 normal, 62 cervical intraepithelial neoplasia (CIN) (31 CIN1 and 31 CIN3) and 63 invasive cancers including 56 squamous cell carcinomas and 7 adenocarcinomas.ResultsThe expression of GSK3β increased in parallel with the lesion grade, while that of cyclin D1 decreased with severity of the lesion (P<0.001). There was a significant inverse correlation between GSK3β and cyclin D1 expression in overall cervical neoplasia (Φ=-0.413, P<0.001). GSK3β expression was higher in squamous cell carcinoma than in adenocarcinoma (P=0.049).ConclusionThese results suggest that the expressional increase in GSK3β plays a role in cervical carcinogenesis and has inverse correlation with cyclin D1 expression in this process. In addition, GSK3β expression appears to be associated with the histologic type of cervical cancer, especially squamous cell carcinoma.

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“…EMT, a highly conserved biological process leading to the induction of invasive growth and metastasis formation, has intensively been studied and is described for multiple cancers, including cervical cancer [26–28]. On the molecular level, EMT is marked by an increased expression of vimentin, a reorganization of the actin cytoskeleton and downregulation of E-cadherin with a switch to higher levels of N-cadherin [29, 30].…”

Section: Introductionmentioning

confidence: 99%

Identification of SEC62 as a potential marker for 3q amplification and cellular migration in dysplastic cervical lesions

et al. 2016

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BackgroundChromosome 3 amplification affecting the 3q26 region is a common genomic alteration in cervical cancer, typically marking the transition of precancerous intraepithelial lesions to an invasive phenotype. Though potential 3q encoded target genes of this amplification have been identified, a functional correlation of potential oncogenic function is still missing. In this study, we investigated copy number changes and the expression level of SEC62 encoded at 3q26.2 as a new potential 3q oncogene in dysplastic cervical lesions and analyzed its role in cervical cancer cell biology.MethodsExpression levels of Sec62 and vimentin were analyzed in liquid based cytology specimens from 107 women with varying grades of cervical dysplasia ranging from normal cases to cancer by immunofluorescence cytology. Additionally, a subset of 20 representative cases was used for FISH analyses targeting SEC62. To further explore the functional role of Sec62 in cervical cancer, HeLa cells were transfected with a SEC62 plasmid or SEC62 siRNA and analyzed for their proliferation and migration potential using real-time monitoring and trans-well systems as well as changes in the expression of EMT markers.ResultsFISH analyses of the swabbed cells showed a rising number of SEC62 gains and amplifications correlating to the grade of dysplasia with the highest incidence in high grade squamous intraepithelial lesions and squamous cell carcinomas. When analyzing the expression level of Sec62 and vimentin, we found a gradually increasing expression level of both proteins according to the severity of the dysplasia. In functional analyses, SEC62 silencing inhibited and SEC62 overexpression stimulated the migration of HeLa cells with only marginal effects on cell proliferation, the expression level of EMT markers and the cytoskeleton structure.ConclusionsOur study suggests SEC62 as a target gene of 3q26 amplification and a stimulator of cellular migration in dysplastic cervical lesions. Hence, SEC62 could serve as a potential marker for 3q amplification, providing useful information about the dignity and biology of dysplastic cervical lesions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2739-6) contains supplementary material, which is available to authorized users.

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Cyclin D1, E‐cadherin and beta‐catenin expression in FIGO Stage IA cervical squamous carcinoma: diagnostic value and evidence for epithelial–mesenchymal transition

Abstract: Most superficially invasive cervical squamous carcinomas show immunophenotypical changes consistent with EMT. These alterations, particularly cyclin D1 expression, may be useful diagnostically. Similar changes in CIN 3 lesions may indicate the acquisition of increased invasive potential.

Cited by 30 publications

References 37 publications

Epithelial-mesenchymal transition-like events in vulvar cancer and its relation with HPV

Epithelial-mesenchymal transition-like events in vulvar cancer and its relation with HPV

Glycogen synthase kinase 3β and cyclin D1 expression in cervical carcinogenesis

Identification of SEC62 as a potential marker for 3q amplification and cellular migration in dysplastic cervical lesions

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