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Identifier

000349827

Title

Μοριακή ανίχνευση και προγνωστική σημασία της ανάλυσης πολλαπλών δεικτών μικρομεταστατικής νόσου (CK19, Mammaglobin-A, HER2) στο αίμα ασθενών με χειρουργήσιμο καρκίνο του μαστού

Author

Ιγνατιάδης, Μιχαήλ Γεωργίου

Thesis advisor

Μαυρουδής, Δημήτρης

Reviewer

Σαμώνης, Γεώργιος
Στουρνάρας, Χρήστος
Θεοδωρόπουλος, Παναγιώτης
Αγγελάκη, Σοφία

Abstract

Purpose: To investigate the prognostic value of the molecular detection of Circulating Tumor Cells (CTCs) using 3 markers [Cytokeratin(CK) 19, Mammaglobin A (MGB1) and HER2] in early breast cancer. Experimental design: CK19mRNA+, MGB1mRNA+, and HER2mRNA+ cells, were detected using real-time (CK19) and nested (MGB1 and HER2) RT-PCR, in the peripheral blood of 175 women with stage I-III breast cancer before the initiation of adjuvant chemotherapy. CTCs’ detection was correlated with clinical outcome. In 10 patients, immunofluoresence staining experiments were performed to investigate the co-expression of CK, MGB1 and HER2 in CTCs. Results: CK19mRNA+, MGB1mRNA+ and HER2mRNA+ cells were detected in 41.1%, 8% and 28.6% of the 175 patients, respectively. Patients had one of the following molecular profiles: CK19mRNA+/MGB1mRNA+/HER2mRNA+ (n=8), CK19mRNA+/MGB1mRNA+/HER2mRNA- (n=1), CK19mRNA+/MGB1mRNA- /HER2mRNA+ (n=42), CK19mRNA+/MGB1mRNA-/HER2mRNA- (n=21), CK19mRNA-/MGB1mRNA+/HER2mRNA- (n=5), CK19mRNA-/MGB1mRNA- /HER2mRNA- (n=98). Double immunofluoresence experiments confirmed the following CTC phenotypes: CK+/MGB1+, CK+/MGB1-, CK-/MGB1+, CK+/HER2+, CK+/HER2-, MGB1+/HER2- and MGB1+/HER2+. In univariate analysis, the detection of CK19mRNA+, MGB1mRNA+ and HER2mRNA+ cells was associated with shorter disease-free survival (DFS), (p<0.001, p=0.001 and p<0.001, respectively), whereas the detection of CK19mRNA+ and MGB1mRNA+ cells was associated with worse overall survival (p=0.044 and p=0.034, respectively). In multivariate analysis, estrogen receptor-negative tumors and the detection of CK19mRNA+ and MGB1mRNA+ cells were independently associated with worse DFS. Conclusion: The detection of peripheral blood CK19mRNA+ and MGB1mRNA+ cells before adjuvant chemotherapy predicts poor DFS in women with early breast cancer.

Physical description

158 σ. : πιν. ; 30 εκ.

Language

Greek

Subject

Breast Neoplasms drug therapy

Issue date

2008-07-30

Collection

School/Department--School of Medicine--Department of Medicine--Doctoral theses

Type of Work--Doctoral theses

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