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. 2013 Nov 4:13:520.
doi: 10.1186/1471-2407-13-520.

High expression of ezrin predicts poor prognosis in uterine cervical cancer

Affiliations

High expression of ezrin predicts poor prognosis in uterine cervical cancer

Jienan Kong et al. BMC Cancer. .

Abstract

Background: Ezrin, a member of the ezrin/radixin/moesin (ERM) protein family, plays a pivotal role in tumor invasion and metastasis. This study is aimed to investigate the clinicopathological significance of upregulated ezrin protein expression in uterine cervical cancers.

Methods: Immunohistochemical staining of ezrin protein was performed on uterine cervical cancer specimens from 235 patients. For comparison, 239 cases of cervical intraepithelial neoplasia (CIN), 17 cases of cervical glandular intraepithelial neoplasia (CGIN) and 52 normal cervix samples were also included. qRT-PCR was performed on fresh tissues to detect ezrin mRNA expression levels. HPV infection statuses were genotyped by oligonucleotide microarray, and 10-year survival rates were calculated using the Kaplan-Meier method for 109 cervical cancer patients.

Results: Apical membranous distribution of ezrin protein was only observed in normal cervical glands, while perinuclear staining was only observed in cervical cancers. Strong cytoplasmic and diffuse localization of ezrin were frequently seen in the cervical cancers compared with the normal counterparts. Furthermore, this strongly positive ezrin expression was significantly higher in cervical cancers than in CIN, CGIN, and normal cervical epithelia. Ezrin overexpression was closely related with poor differentiation, late stage, and lymph node metastasis. Additionally, ezrin overexpression was associated with lower 10-year survival rate for patients with early stage cervical cancer, but not for patients with advanced stage.

Conclusions: Aberrant localization and overexpression of ezrin might be an independent effective biomarker for prognostic evaluation of cervical cancers.

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Figures

Figure 1
Figure 1
Ezrin protein expression and localization in uterine cervical lesions. (A) Ezrin protein was not expressed in normal cervical squamous epithelia, but showed strongly positive staining in the lymphocytes of the cervical stroma. (B) Scattered cells positive for ezrin were observed in normal glands; expression was concentrated at the apical membranes (arrows). (C) Ezrin protein was strongly expressed in the atypical glandular cells of CGIN, but was negative in the adjacent normal squamous epithelia. (D) Ezrin was expressed in the atypical cells of CIN-3, but not in the adjacent normal glandular cells. (E) Ezrin protein was strongly expressed in the cytoplasm of cervical squamous cell carcinomas and also exhibited perinuclear staining (arrows) (insert). (F) Ezrin protein was strongly expressed in the cytoplasm of cervical adenocarcinomas. (Original magnification, 200× in A–F, and 400× in insert).
Figure 2
Figure 2
Immunohistochemical staining for ezrin in tissue arrays of cervical lesions. (A) Ezrin was not expressed in cervical squamous cell carcinoma. (B) Scattered apical membranous staining pattern (arrows) was observed in normal cervical glands. (C) Ezrin was moderately expressed in the cytoplasm of cervical adenocarcinoma cells. (D) Moderate ezrin expression in the invasive cancer loci (arrows) of cervical squamous cell carcinoma. (Original magnification, 200× in A–D).
Figure 3
Figure 3
qRT-PCR analysis of ezrin mRNA expression in normal cervical epithelia and cervical cancers. Experiments were performed in triplicate for each case. Ezrin mRNA expression levels were significantly higher in cervical squamous cell carcinomas and adenocarcinomas compared with normal cervical epithelia fresh tissues.
Figure 4
Figure 4
Kaplan-Meier survival curves illustrating the significance of ezrin expression in early-stage uterine cervical cancers. In early-stage cervical cancers (stages I–IIA, n=51), patients with high ezrin expression had significantly reduced cervical cancer-specific 10-year survival rates relative to those with low ezrin expression (log rank P=0.030).

References

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