Oscar Del Moral-Hernández1, Daniel Hernández-Sotelo2, Luz Del Carmen Alarcón-Romero3, Miguel Angel Mendoza-Catalán4, Eugenia Flores-Alfaro5, Yaneth Castro-Coronel3, Julio Ortiz-Ortiz4, Marco Antonio Leyva-Vázquez4, Carlos Ortuño-Pineda4, Wendy Castro-Mora3, Berenice Illades-Aguiar6,7. 1. Laboratorio de Virología, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, Mexico. 2. Laboratorio de Epigenética del Cáncer, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, Mexico. 3. Laboratorio de Citopatología e Histoquímica, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, Mexico. 4. Laboratorio de Biomedicina Molecular, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, Mexico. 5. Laboratorio de Epidemiologia Clínica y Molecular de la Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, Mexico. 6. Laboratorio de Biomedicina Molecular, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, Mexico. b.illadesaguiar@gmail.com. 7. Av. Lázaro Cárdenas S/N, Ciudad Universitaria, Facultad de Ciencias Químico Biológicas, 39090, Chilpancingo, Guerrero, Mexico. b.illadesaguiar@gmail.com.
Abstract
BACKGROUND: To improve the efficiency of early diagnosis systems for cervical cancer, the use of cellular and viral markers for identifying precancerous lesions with a greater probability to progress to cancer has been proposed. Several cellular proteins and markers of oxidative DNA damage have been suggested as possible biomarkers of cervical carcinogenesis; however, they have not been evaluated together. In this study, we analyzed the expression of the cellular markers p16INK4a, Ki-67, CyclinE1, TOP2A/MCM2, and telomerase, as well as the DNA oxidative damage markers ROS and 8-OHdG. The analyses were performed in liquid-based cervical cytology samples or biopsies with premalignant lesions or cervical cancer diagnosis, with the purpose of selecting a panel of biomarkers that allow the identification of precursor lesions with greater risk of progression to cervical cancer. METHODS: We analyzed 1485 liquid-based cytology samples, including 239 non-squamous intraepithelial lesions (NSIL), 901 low-grade squamous intraepithelial lesions (LSIL), 54 high-grade squamous intraepithelial lesions (HSIL), and 291 cervical cancers (CC). The biomarkers were analyzed by immunocytochemistry and Human Papilloma Virus (HPV) genotyping with the INNO-LiPA genotyping Extra kit. RESULTS: We found that all tested cellular biomarkers were overexpressed in samples with high risk-HPV infection, and the expression levels increased with the severity of the lesion. TOP2A/MCM2 was the best biomarker for discriminating between LSIL and HSIL, followed by p16INK4a and cyclinE1. Statistical analysis showed that TOP2A/MCM2 provided the largest explanation of HSIL and CC cases (93.8%), followed by p16INK4a (91%), cyclin E1 (91%), Ki-67 (89.3%), and telomerase (88.9%). CONCLUSIONS: We propose that the detection of TOP2A/MCM2, p16INK4a and cyclin E1 expression levels is useful as a panel of biomarkers that allow identification of cervical lesions with a higher risk for progression to CC with high sensitivity and precision; this can be done inexpensively, in a single and non-invasive liquid-based cytology sample.
BACKGROUND: To improve the efficiency of early diagnosis systems for cervical cancer, the use of cellular and viral markers for identifying precancerous lesions with a greater probability to progress to cancer has been proposed. Several cellular proteins and markers of oxidative DNA damage have been suggested as possible biomarkers of cervical carcinogenesis; however, they have not been evaluated together. In this study, we analyzed the expression of the cellular markers p16INK4a, Ki-67, CyclinE1, TOP2A/MCM2, and telomerase, as well as the DNA oxidative damage markers ROS and 8-OHdG. The analyses were performed in liquid-based cervical cytology samples or biopsies with premalignant lesions or cervical cancer diagnosis, with the purpose of selecting a panel of biomarkers that allow the identification of precursor lesions with greater risk of progression to cervical cancer. METHODS: We analyzed 1485 liquid-based cytology samples, including 239 non-squamous intraepithelial lesions (NSIL), 901 low-grade squamous intraepithelial lesions (LSIL), 54 high-grade squamous intraepithelial lesions (HSIL), and 291 cervical cancers (CC). The biomarkers were analyzed by immunocytochemistry and Human Papilloma Virus (HPV) genotyping with the INNO-LiPA genotyping Extra kit. RESULTS: We found that all tested cellular biomarkers were overexpressed in samples with high risk-HPV infection, and the expression levels increased with the severity of the lesion. TOP2A/MCM2 was the best biomarker for discriminating between LSIL and HSIL, followed by p16INK4a and cyclinE1. Statistical analysis showed that TOP2A/MCM2 provided the largest explanation of HSIL and CC cases (93.8%), followed by p16INK4a (91%), cyclin E1 (91%), Ki-67 (89.3%), and telomerase (88.9%). CONCLUSIONS: We propose that the detection of TOP2A/MCM2, p16INK4a and cyclin E1 expression levels is useful as a panel of biomarkers that allow identification of cervical lesions with a higher risk for progression to CC with high sensitivity and precision; this can be done inexpensively, in a single and non-invasive liquid-based cytology sample.
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Authors: M I Zubillaga-Guerrero; B Illades-Aguiar; M A Leyva-Vazquez; E Flores-Alfaro; E Castañeda-Saucedo; J F Muñoz-Valle; L C Alarcón-Romero Journal: J Cytol Date: 2013-01 Impact factor: 1.000