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Role of circulating molecular biomarkers in solid tumors

Capizzi, Elisa (2012) Role of circulating molecular biomarkers in solid tumors, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Oncologia e patologia sperimentale: progetto n. 2 "Patologia sperimentale", 24. Ciclo.

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Background: Circulating tumor cells (CTCs) and circulating free plasma DNA (FPDNA) have been proposed as biomarkers predictive of outcome and response to therapy in solid tumors. We investigated the multiple associations of the presence of CTC and the levels of FPDNA with the outcome and/or the response to chemotherapy in patients with localized breast cancer (LBC), metastatic breast cancer (MBC) and advanced ovarian cancer (AOC). Experimental Design: Blood samples were collected before (baseline), during and after therapy in 40 LBC and 50 AOC patients treated with neo-adjuvant chemotherapy. In 20 MBC patients blood was sampled at baseline and every each cycle of adjuvant chemotherapy. Real time PCR was applied to quantify FPDNA using the Quantifiler Human Quantification kit and CTCs through the detection of tumor-cell specific mRNA levels with or without epithelial enrichment. Results: At baseline CTCs were detected in 90% MBC, 42.5% LBC and 33% AOC patients respectively. The presence of baseline CTC was significantly associated with shorter overall survival (OS) in MBC and AOC patients, and shorter progression free survival (PFS) in LBC patients. Presence of CTCs at the end of neo-adjuvant chemotherapy was detected in 42% LBC and 18% AOC patients and was associated with shorter PFS and OS only in LBC. Increased FPDNA levels at baseline were found in 65% MBC, 17.5% LBC and 76% AOC patients but never related to OS. Baseline FPDNA high levels were associated with shorter PFS only in LBC patients. High FPDNA levels after neo-adjuvant chemotherapy were detected in 57% LBC and 48% AOC patients. Increased FPDNA after neo-adjuvant was associated with response to therapy and shorter PFS in AOC patients. Conclusions: Detection of CTCs may represent a prognostic and predictive biomarker in LBC, MBC and AOC. Quantification of FPDNA could be useful for monitoring response to therapy in AOC patients.

Tipologia del documento:Tesi di dottorato
Autore:Capizzi, Elisa
Relatore:Derenzini, Massimo
Dottorato di ricerca:Oncologia e patologia sperimentale: progetto n. 2 "Patologia sperimentale"
Scuola di dottorato:Scienze biologiche, biomediche e biotecnologiche
Coordinatore:Grilli, Sandro
Settore disciplinare:Area 06 - Scienze mediche > MED/05 Patologia clinica
Settore concorsuale:Area 06 - Scienze mediche > 06/A - Patologia e diagnostica di laboratorio
Parole chiave:CTC, FPDNA, marcatori circolanti, carcinoma mammella, carcinoma ovarico
Data di discussione:03 Maggio 2012

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