|Titel:||Detektion, Charakterisierung und prognostische Relevanz von zirkulierenden Tumorzellen im Blut von Patientinnen mit Vulvakarzinom||Sonstige Titel:||Detection, characterisation and prognostic relevance of circulating tumour cells in the bloodstream of patients with vulvar carcinoma||Sprache:||Deutsch||Autor*in:||Schmidbauer, Svenja||Schlagwörter:||CTC; zirkulierende Tumorzellen; vulvar carcinoma; CTC; circulating tumour cells||GND-Schlagwörter:||Vulvakrebs||Erscheinungsdatum:||2016||Tag der mündlichen Prüfung:||2016-09-13||Zusammenfassung:||
Circulating tumour cells (CTC) play a crucial role in the process of metastatic spread. They are used as a prognostic marker for several tumour entities. Vulvar carcinoma is a relative rare tumour entity; yet, its incidence increases considerably especially among younger women. There is currently no standard treatment which determines the extent of surgery or the application of adjuvant therapies. In order to improve the prediction of the prognosis and therefore guide treatment decisions, numerous molecular markers have been investigated. Most of vulvar squamous cell carcinomas (VSCC) express the epithelial growth factor receptor (EGFR), which could be of prognostic value. In addition therapy trials with EGFR inhibitors have been successful. In this thesis, I investigated if CTC are detectable in patients with VSCC using well-established methods, if their detection correlates with histopathological parameters, and if this has any prognostic value, as well as whether CTC express EGFR.
Peripheral blood samples from 52 patients (initial diagnosis and relapse) were analyzed before surgery. Separation of mononuclear cells was carried out using a density gradient centrifugation system. Pancytokeratin antibodies were used for detection with light microscope and APAAP-staining, and combined with EGFR for dual immunofluorescence staining.
CTC were detectable in 12.8% of all VSCC cases, more frequently in patients with recurrent carcinoma. It can thus be assumed that CTC are relevant for the emergence of tumour relapse. CTC were more often present when the tumour affected blood or lymphatic vessels, as well as in cases of distant metastases. It therefore seems that the detection of CTC in VSCC patients indicates a systemic spread of the disease. Moreover CTC occurred more frequently when several types of dysplasia adjacent to the tumour were present, which could possibly facilitate the access of tumour cells to the bloodstream. CTC were also more often detectable in patients with progressive disease and among the patients who died from vulvar cancer. If this could be confirmed in larger studies, the detection of CTC could supplement existing diagnostic tools. A total of six potential CTC and EGFR+ objects were detected. None of them could be definitely identified as CTC. Indeed, most of them were positive for cytokeratins (CK) but lacked completely or partly a cell nucleus. These are probably apoptotic cells, which might also prove to be of prognostic relevance. The EGFR+/CK- object detected might be a cell undergoing EMT. To confirm this, both epithelial und mesenchymal markers should be used. The CTC detected in the blood of a patient with VIN was probably a benign epithelial cell. When using only epithelial specific markers, it should be considered that there might be false positive results in case of benign inflammatory lesions.
|URL:||https://ediss.sub.uni-hamburg.de/handle/ediss/6914||URN:||urn:nbn:de:gbv:18-81289||Dokumenttyp:||Dissertation||Betreuer*in:||Pantel, Klaus (Prof. Dr.)|
|Enthalten in den Sammlungen:||Elektronische Dissertationen und Habilitationen|
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