Detection of gene promoter hypermethylation in fine needle washings from breast lesions

• Type: Article in International Scientific Journal
• Date: 2003

Authors

Carmen Jeronimo (Author) Other; Costa, I (Author) Other; Martins, MC (Author) Other; Monteiro, P (Author) Other; Lisboa, S (Author) Other; Palmeira, C (Author) Other; henrique, rmf (Author) ICBAS; Manuel R Teixeira (Author) ICBAS; Lopes, C (Author) Other

Journal

Title: Clinical Cancer Research

Vol. 9

Pages: 3413-3417

ISSN: 1078-0432

Publisher: American Association for Cancer Research

Indexing

ISI Web of Knowledge - 56 Citations

Scopus - 67 Citations

Other information

Authenticus ID: P-000-FHW

Abstract (EN): Purpose: Fine needle aspiration (FNA) is used widely in diagnostic assessment of breast lesions. However, cytomorphological evaluation depends heavily on the proficiency of cytopathologists. Because epigenetic alterations are frequent and specific enough to potentially augment the accuracy of malignant disease detection, we tested whether hypermethylation analysis of a panel of genes would distinguish benign from malignant breast FNA washings. Experimental Design: FNA washings were collected from 123 female patients harboring suspicious mammary lesions. Sodium bisulrite-modified DNA was amplified by methyl-specific PCR (MSP) for CDH1, GSTP1, BRCA1, and RARbeta to detect gene promoter CpG island methylation. Paired samples of 27 breast cancer tissue and 7 fibroadenomas and 12 samples of normal breast tissue, collected post-operatively, were also analyzed. MSP results were compared with conventional cytomorphological diagnosis. Results: FNAs were cytomorphologically diagnosed as benign (25 cases), malignant (76 cases), suspicious for malignancy (6 cases), and unsatisfactory (16 cases). Percentages of methylated CDH1, GSTP1, BRCA1, and RARbeta in FNA washings were 60, 52, 32, and 16%, and 65.8, 57.9, 39.5, and 34.2% for benign and malignant lesions, respectively. These differences did not reach statistical significance. In all of the paired benign lesions tested, there was absolute concordance. Sixty-seven percent (18 of 27) of FNA washings displayed hypermethylation patterns identical to malignant paired tissue. No methylation was found in the normal breast samples for any of the genes. Conclusions: Detection of gene hypermethylation in FNA washings by MSP analysis is feasible, but the selected gene panel does not discriminate between benign and malignant breast lesions.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 5