Quantitative hypermethylation of a small panel of genes augments the diagnostic accuracy in fine-needle aspirate washings of breast lesions
| Autor: | André Lopes Carvalho, Carmen Jerónimo, Rui Henrique, C. Leal, Isabel Costa, Mário Dinis-Ribeiro, Mohammad O. Hoque, Luísa Filipe, Manuel R. Teixeira, Paula Monteiro, Irene Pais, Vera Costa, David Sidransky |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Cancer Research medicine.medical_specialty Pathology Biopsy Biopsy Fine-Needle Breast Neoplasms Epigenesis Genetic GSTP1 Breast cancer Biomarkers Tumor medicine Humans Sulfites Promoter Regions Genetic skin and connective tissue diseases Aged Aged 80 and over medicine.diagnostic_test business.industry Cancer Anatomical pathology DNA Methylation Middle Aged medicine.disease Gene Expression Regulation Neoplastic Fine-needle aspiration Oncology Female Cancer biomarkers Breast disease business |
| Zdroj: | Breast Cancer Research and Treatment. 109:27-34 |
| ISSN: | 1573-7217 0167-6806 |
| DOI: | 10.1007/s10549-007-9620-x |
| Popis: | We hypothesized that comprehensive breast cancer methylation profiling might provide biomarkers for diagnostic assessment of suspicious breast lesions using fine needle aspiration biopsy (FNA).Twenty-three gene promoters were surveyed by quantitative methylation-specific PCR in bisulfite-modified DNA from 66 breast carcinomas (BCa), 31 fibroadenomas (FB) and 12 normal breast (NT) samples to define a set of genes differentially methylated in malignant and non-malignant tissues. This set was tested in 78 FNA washings obtained pre-operatively (66 malignant, 12 benign), with histopathological diagnosis. Receiver operator characteristic (ROC) curve analysis identified a gene panel which might distinguish cancer from non-cancerous lesions. Finally, this panel was validated in an independent series of FNA washings (45 cases) in which cytomorphology did not reach definitive diagnosis.In tissue samples, 14-3-3-sigma, DAPK, CCND2, RASSF1A, CALCA, APC, HIN1, RARbeta2, TIG1, and GSTP1 methylation levels differed significantly among BCa, FB, and NT. ROC curve analysis identified a panel of four gene loci (CCND2, RASSF1A, APC, and HIN1) that discriminated BCa from benign lesions in a set of 78 FNA washings from histologically characterized breast lesions. When this panel was tested in the validation dataset of 45 FNA washings, breast cancer was identified with perfect specificity (100%) when 3 of 4 gene loci tested positive, providing estimated added information of 91% over cytomorphologic evaluation alone.Our data provide evidence that multigene methylation analysis augments diagnostic accuracy of cytological assessment of suspicious breast lesions, and might be a valuable ancillary tool for breast cancer diagnosis. |
| Databáze: | OpenAIRE |
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