Abstract
BackgroundCervical cancer (CC) is the fourth cause of mortality by neoplasia in women worldwide. The use of immunomarkers is an alternative tool to complement currently used algorithms for detection of cancer, and to improve selection of therapeutic schemes. Aberrant expression of Ezrin and E-cadherin play an important role in tumor invasion. In this study we analyzed Ezrin and E-cadherin expression in liquid-based cervical cytology samples, and evaluated their potential use as prognostic immunomarkers.MethodsImmunocytochemical staining of Ezrin and E-cadherin was performed in cervical samples of 125 patients. The cytological or histological diagnostic was performed by Papanicolaou staining or H&E staining, respectively. HPV genotyping was determined using INNO-LIPA Genotyping Extra kit and the HPV physical status by in situ hybridization. Ezrin expression in HaCaT, HeLa and SiHa cell lines was determined by immunocytochemistry, immunofluorescence and Western blot.ResultsHigh Ezrin expression was observed in cervical cancer samples (70%), samples with multiple infection by HR-HPV (43%), and samples with integrated viral genome (47%). High Ezrin expression was associated with degree of SIL, viral genotype and physical status. In contrast, low E-cadherin expression was found in cervical cancer samples (95%), samples with multiple infection by HR-HPV/LR-HPV (87%) and integrated viral genome (72%). Low E-cadherin expression was associated with degree of SIL and viral genotype. Interestingly, Ezrin nuclear staining was associated with degree of SIL and viral genotype. High Ezrin expression, high percent of nuclear Ezrin and low E-cadherin expression behaved as risk factors for progression to HSIL and cervical cancer.ConclusionsEzrin and E-cadherin expression profile in cervical cytology samples could be a potential prognostic marker, useful for identifying cervical lesions with a high-risk of progression to cervical cancer.
Highlights
Cervical cancer (CC) is the fourth cause of mortality by neoplasia in women worldwide
We evaluated the prognostic value of Ezrin and E-cadherin expression on cervical cytology, as well as its relationship with the genotype and physical status of HPV for the screening of cervical lesions
We found that high Ezrin and low E-cadherin expression implicate 4.61 and 6. 14 times more risk, respectively, for developing HSIL or CC (Table 4), suggesting that combined determination of Ezrin and E-cadherin expression could be useful for assessing the prognosis of patients
Summary
Cervical cancer (CC) is the fourth cause of mortality by neoplasia in women worldwide. The use of immunomarkers is an alternative tool to complement currently used algorithms for detection of cancer, and to improve selection of therapeutic schemes. In this study we analyzed Ezrin and E-cadherin expression in liquid-based cervical cytology samples, and evaluated their potential use as prognostic immunomarkers. Cervical cancer (CC) is the fourth cause of death by neoplasms in women worldwide, with a mortality rate of 6.8 per 100,000 women. In Mexico, CC is the second cause of death by cancer in women, with a mortality rate. Colposcopy and the Papanicolaou staining (Pap test) in liquid-based cytology are the first line screening methods for the early detection of cervical cancer and premalignant lesions [2]. Implementation of molecular and cellular biology techniques has improved the specificity and sensitivity of diagnosis, prognosis and treatment of cervical cancer.
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