Unit:
Τομέας ΧειρουργικήςLibrary of the School of Health Sciences
Author:
Αλεβίζος Λεωνίδας
Dissertation committee:
Γεώργιος Ζωγράφος, Ανδρέας Μανουράς, Μανούσος Κωνσταντουλάκης (επιβλέπων)
Original Title:
Ανίχνευση λεμφαδενικών μικρομεταστάσεων σε ασθενείς με καρκίνο του μαστού.
Summary:
Purpose: To determine whether the methylation profile found in breast cancer
characterises cancer cells after their dispersion in lymph nodes and whether it
can be used as molecular marker to detect malignancy and predict metastatis.
Materials and methods: The methylation signatures of 5 cancer-related genes
were evaluated in 30 breast cancer lesions and their matching positive/negative
lymph nodes. Eight adenomas served as controls. The implication of methylation
in CXCR4 and Caveolin-1 gene expression was further assessed by
immunohistochemistry.
Results: The methylation profiles of any two genes within the triplet
RAR-β/Cyclin D2/Twist accurate markers for the detection of breast malignancy.
Methylation patterns were highly preserved between primary tumour and positive
lymph nodes. The percentage of agreement was lower for negative lymph nodes.
Hence metastasis-free lymph nodes could not be accurately identified.
Methylation phenotypes of CXCR4 and Caveolin-1 genes were associated with their
protein levels. Lack of CXCR4 M/M pattern, presence of Caveolin-1 M/M pattern
and absence of stromal Caveolin-1 expression were linked to nodal metastasis.
Caveolin-1 expression in tumour cells was associated with relapse.
Conclusion: These results implied that DNA methylation is a significant
regulator of gene expression and as such it has an important role in the
biology of metastasis.
Keywords:
methylation, metastasis, breast cancer, CXCR4, Caveolin-1
Number of references:
114
