RESUMEN
BACKGROUND: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are a promising prognostic biomarker of gliomas. The purpose of our study was to examine the clinical prognostic properties of IDH1/2 mutations in a glioma patient cohort from the Czech Republic using an improved platform for simple and reliable IDH genotyping. MATERIAL AND METHODS: We retrospectively analyzed a group of 145 glioma patients by testing for the three most frequent IDH mutations, IDH1 R132H, IDH1 R132C, and IDH2 R172K, through the competitive amplification of differentially melting amplicons (CADMA) polymerase chain reaction (PCR). O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, copy number of EGFR, p53, RB1, MDM2, CDKN2A genes, and deletions in 1p, 19q and 10p chromosomal regions were also analyzed and correlated with clinical characteristics. RESULTS: Of 145 gliomas, 36 harbored IDH1 R132H mutation and 1 IDH1 R132C mutation. We did not detect any IDH2 R172K mutation. IDH1 mutations were positively associated with MGMT methylation (OR 3.08, 95% CI 1.387-7.282; p = 0.007), 1p/19q co-loss (OR 8.85, 95% CI 2.367-42.786; p = 0.002) and negatively associated with epidermal growth factor receptor amplification (OR 0.12, 95% CI 0.019-0.437; p = 0.006) and 10p loss (OR 0.09, 95% CI 0.005-0.436; p = 0.019). The overall survival of IDH-mutant was 25 months, but only 9 months in IDH-wild type gliomas (p = 0.035); at the same time, survival associated with methylated vs. unmethylated MGMT promoter did not significantly differ (p = 0.166). CONCLUSION: Despite IDH1 mutations being closely associated with MGMT methylation in glioma patients, IDH1 mutations in glioblastoma patients are stronger marker of overall survival than MGMT methylation and should be the marker of choice, especially when using genotyping by CADMA PCR.Key words: isocitrate dehydrogenase - polymerase chain reaction - glioma - glioblastoma.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Glioma/genética , Isocitrato Deshidrogenasa/genética , O(6)-Metilguanina-ADN Metiltransferasa/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Metilación de ADN , Femenino , Glioma/mortalidad , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Regiones Promotoras Genéticas , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To get initial experience with alternative sampling (self-sampling) for HPV testing as the means of cervical cancer screening program. DESIGN: Original work. SETTING: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc. METHODS: Based on expression of interest, 215 self-sampling kits were posted to women. Evalyn(®) Brush Vaginal swabs obtained by self-sampling were analyzed for the presence of HPV infection by Cobas 4800 HPV (Roche) followed by genotyping using PapilloCheck(®) HPV-Screening (Greiner Bio-One). Sixty women randomly chosen from our sample were sent a questionnaire focused on their experience with self-sampling. RESULTS: One hundred seventy-four of 215 (81%) distributed self-sampling devices have been delivered to analysis. All cervicovaginal swabs were sampled correctly and it was possible to analyze them by Cobas 4800 HPV test. Similarly, 98% (171/174) samples were analyzable by PapilloCheck(®) HPV-Screening.One hundred twenty-five (72%) of 174 tested samples were HPV negative. Low risk HPV infection was detected only in 7 samples (4%), and high risk HPV (hrHPV) infection was present in 42 samples (24%). The most frequently detected hrHPV genotypes were HPV16 (11/42; 26%) and HPV53 (6/42; 14%). HrHPV co-infection was detected in 10 cases, in 5 of them lrHPV infection was find also.Of the 60 questionnaires, 48 (80%) were returned. From this group, 47 (98%) women rated their experience with self-sampling device as good to excellent. User manual of self-sampling device was considered good to excellent by all women (100%). All women also rated the convenience of self-sampling device using as good to excellent. As expected, most of the women (n = 42 [88%]) preferred self-sampling to physician sampling. CONCLUSION: Cervicovaginal self-sampling leads to valid results of HPV screening using two molecular genetics methods and was accepted by Czech women very well. The self-sampling as an opportunity to participate in cervical cancer screening could increase the attendance of the screening program and would help to reduce the incidence and mortality for this disease in the Czech population.
Asunto(s)
Detección Precoz del Cáncer/métodos , Infecciones por Papillomavirus/diagnóstico , Autocuidado/métodos , Neoplasias del Cuello Uterino/prevención & control , Frotis Vaginal/métodos , Adulto , Femenino , Genotipo , Papillomavirus Humano 16 , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/virología , Aceptación de la Atención de Salud , Satisfacción del Paciente , Proyectos Piloto , Manejo de Especímenes , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To describe the possibility of detection of HPV DNA in cervical cancer. DESIGN: Review. SETTING: Institute of Molecular and Translational Medicine, Laboratory of Experimental Medicine, Palacky University and University Hospital Olomouc. METHODS: Human papillomavirus (HPV) is the cause of many cancers, especially cervical cancer. Current cervical cancer screening is based on cytological examination, which is followed by HPV DNA diagnostics only in cases with abnormal results of uncertain significance. Methods used for HPV detection are often based on PCR reaction followed by genotyping (complete or partial). HPV DNA diagnostics isn´t currently included into the primary cervical cancer screening in the Czech Republic although it has higher sensitivity than cytology. CONCLUSION: Inclusion of HPV DNA testing into the primary cervical cancer screening would significantly increase its sensitivity and thus would help to reduce the morbidity and mortality of this disease in Czech population.