Résumé
OBJECTIVE: DNA methylation has been shown to be a potential biomarker for early cancer detection. The aim of this study was to evaluate DNA methylation profiles according to liquid-based Pap (LBP) test results and to assess their diagnostic value in a Korean population. METHODS: A total of 205 patients with various Papanicolaou test results were enrolled to this study (negative, 26; atypical squamous cells of undetermined significance, 39; low grade squamous intraepithelial lesion, 44; high grade squamous intraepithelial lesion (HSIL), 48; and cancer, 48). DNA methylation analysis of four genes, ADCYAP1, PAX1, MAL, and CADM1, was performed on residual cervical cells from LBP samples using a quantitative bisulfite pyrosequencing method. To evaluate the diagnostic performance of the four methylated genes for cancer detection, receiver operating characteristic (ROC) curves were drawn. Sensitivities and specificities were also tested at cutoffs determined from the ROC curves. RESULTS: Cervical cancer cells showed dramatically increased methylation levels for the four genes analyzed. ADCYAP1 and PAX1 also trended toward elevated methylation levels in HSIL samples, although the levels were much lower than those in cancer cells. The sensitivities of methylated ADCYAP1, PAX1, MAL, and CADM1 for the detection of cancer were 79.2%, 75.0%, 70.8%, and 52.1%, and the specificities were 92.0%, 94.0%, 94.7%, and 94.0%, respectively. Methylated ADCYAP1 and PAX1 demonstrated relatively better discriminatory ability than did methylated MAL and CADM1 (area under the curves 0.911 and 0.916 vs. 0.854 and 0.756, respectively). CONCLUSION: DNA methylation status, especially in the ADCYAP1 and PAX1 genes, showed relatively good specificity, ranging from 90% to 94%. The possible additive and complementary roles of DNA methylation testing with respect to conventional cervical cancer screening programs will need to be validated in prospective population-based studies.
Sujets)
Femelle , Humains , Alphapapillomavirus/génétique , Cellules malpighiennes atypiques du col utérin/anatomopathologie , Molécules d'adhérence cellulaire/génétique , Méthylation de l'ADN , Génotype , Immunoglobulines/génétique , Protéines protéolipidiques associées à la myéline et au lymphocyte/génétique , Facteurs de transcription PAX/génétique , Test de Papanicolaou , Polypeptide activateur de l'adénylcyclase hypophysaire/génétique , Courbe ROC , Lésions malpighiennes intra-épithéliales du col utérin/génétique , Tumeurs du col de l'utérus/génétique , Frottis vaginauxRésumé
OBJECTIVE@#To compare the expression pattern of the MAL protein in normal and laryngeal carcinoma to derive possible implications of MAL in carcinoma development of larynx.@*METHOD@#Use the immunohistochemical technique to analyze the distribution of MAL in normal laryngeal epithelial cells, polyp of vocal cords, laryngeal atypical hyperplasia and laryngeal squamous cell carcinoma.@*RESULT@#MAL-like immunohistochemical reactions are strongly expressed in normal laryngeal epithelial cells and its expression is no significantly different in epithelial cells of the polyp of vocal cords. Comparatively, MAL expression is significantly down regulated in laryngeal atypical hyperplasia and laryngeal squamous cell carcinomas (P < 0.05).@*CONCLUSION@#MAL is normally expressed in laryngeal epithelial cells and its expression changes at early stages of carcinoma development. MAL, therefore, is a potential marker for early diagnosis of laryngeal squamous cell carcinoma.