Relative Häufigkeit, Charakterisierung und prognostischer Stellenwert lymphogener Mikrometastasierung beim Magenkarzinom

Wesselhöft, Kai

dc.contributor.advisor	Horstmann, Olaf Prof. Dr.
dc.contributor.author	Wesselhöft, Kai
dc.date.accessioned	2014-06-13T08:15:44Z
dc.date.available	2014-07-02T22:50:04Z
dc.date.issued	2014-06-13
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0022-5EE6-9
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-4546
dc.language.iso	deu	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.ddc	610	de
dc.title	Relative Häufigkeit, Charakterisierung und prognostischer Stellenwert lymphogener Mikrometastasierung beim Magenkarzinom	de
dc.type	doctoralThesis	de
dc.title.translated	Relative frequency, characterization and prognostic significance of lymphatic micrometastasis in gastric cancer	de
dc.contributor.referee	Horstmann, Olaf Prof. Dr.
dc.date.examination	2014-06-25
dc.description.abstracteng	Background: Lymph node micrometastases (MM), not detectable by standard staging methods, may be a reason for poor survival rates of patients with node-negative gastric cancer. Main objectives of this study were the MM detection by immunhistochemistry, further characterization and the assessment of their prognostic relevance. Methods: Regional lymph nodes of 56 pN0 patients were analysed immunohistochemically with the monoclonal antibody Ber-EP4. It labels the epithelial cell adhesion molecule EpCAM which is broadly distributed in epithelial cells and is expressed in most of the carcinomas including gastric cancer cells. Patients with immunoreactive single cells or cell clusters up to 0.2 cm in size were considered MM-positive (MM+). The evaluation of their prognostic influence was performed in uni- and multivariate analysis. In addition, MM were examined with immunohistochemical double staining, which sequentially labelled EpCAM and p53. The p53-status of the MM was compared with the p53-labelling-index of their primary tumor. Results: MM were found in 33 (58.9%) of 56 pN0 patients. The occurence was independant of classic prognostic factors. Compared to the MM-negative subgroup, the reduction of the MM+ patients' 5-year survival rate was almost significant (5-year survival rate MM+ 58%, MM- 82%, p = 0.059). The multivariate analysis identified MM as an independent prognostic factor. In the subsequent double staining, the antigen retrieval rate was only 18.2%. Two of these six patients had p53-positive MM. MM of primary tumors with p53-overexpression showed a heterogenous p53-antigen profile. Conclusion: Ber-EP4-immunoreactive cells are found in lymph nodes in more than half of the histologically node-negative gastric cancers. The study confirms that the used method detects occult tumor cells. The MM are independent of classical prognostic factors and may occur at very early stages of the disease. They impair patients' prognosis even when morphological criteria are excluded. According to the results of the double staining, the accumulation of overexpressed p53 in lymph node MM is variable and a positive p53-overexpression-index of the primary tumor does not predict the p53-status of the MM. The inclusion of histopathological criteria, a detailed immunhistopathological cell characterization and a subdivision in micrometastases and isolated tumor cells should be subjects for further studies. This may lead to a more accurate tumor staging that helps to estimate the patient's course of disease more individually and to establish an optimized stage-adapted therapy in the future.	de
dc.contributor.coReferee	Brembeck, Felix Hermann Prof. Dr.
dc.subject.ger	Magenkarzinom	de
dc.subject.ger	Mikrometastasen	de
dc.subject.ger	Lymphknoten	de
dc.subject.ger	Ber-EP4	de
dc.subject.ger	EpCAM	de
dc.subject.ger	p53	de
dc.subject.eng	gastric cancer	de
dc.subject.eng	lymph node micrometastasis	de
dc.subject.eng	Ber-EP4	de
dc.subject.eng	EpCAM	de
dc.subject.eng	p53	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-0022-5EE6-9-4
dc.affiliation.institute	Medizinische Fakultät	de
dc.subject.gokfull	Chirurgie - Allgemein- und Gesamtdarstellungen (PPN619875968)	de
dc.description.embargoed	2014-07-02
dc.identifier.ppn	788243802

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Human- und Zahnmedizin [2872]

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