Relative Häufigkeit, Charakterisierung und prognostischer Stellenwert lymphogener Mikrometastasierung beim Magenkarzinom

Relative frequency, characterization and prognostic significance of lymphatic micrometastasis in gastric cancer

by Kai Wesselhöft
Doctoral thesis
Date of Examination:2014-06-25
Date of issue:2014-06-13
Advisor:Prof. Dr. Olaf Horstmann
Referee:Prof. Dr. Olaf Horstmann
Referee:Prof. Dr. Felix Hermann Brembeck
Persistent Address: http://dx.doi.org/10.53846/goediss-4546

 

 

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Abstract

English

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.
Keywords: gastric cancer; lymph node micrometastasis; Ber-EP4; EpCAM; p53
Schlagwörter: Magenkarzinom; Mikrometastasen; Lymphknoten; Ber-EP4; EpCAM; p53
 
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