Prädiktive und prognostische Relevanz von p53 und Ki67 beim lokal fortgeschrittenen Rektumkarzinom cUICC-II/III

Immunhistochemische Analysen im methodischen Vergleich

Predictive and prognostic value of p53 and Ki67 in locally advanced rectal cancer cUICC-II/III

Immunohistochemical analysis and comparison of analysis methods

by Susanna Posern
Doctoral thesis
Date of Examination:2013-11-12
Date of issue:2013-10-21
Advisor:PD Dr. Torsten Liersch
Referee:Prof. Dr. Heinz-Joachim Radzun
Referee:Prof. Dr. Matthias Dobbelstein
Referee:Prof. Dr. Martin Oppermann
Persistent Address: http://dx.doi.org/10.53846/goediss-4097

 

 

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Abstract

English

In Germany, colorectal carcinoma represents the second most common cause of death in cancer diseases. The treatment of rectal cancer is stage-dependent and includes a multimodal therapy concept. Currently, the therapeutic regimen for locally advanced rectal cancer involve a neoadjuvant radio-chemotherapy (RCT) followed by the surgical resection of the rectum. Unfortunately approximately 40% of all patients with locally advanced rectal cancer show a poor response to the multimodal therapy. Because of this it is very important to identify an individual risk-profile on the basis of predictive and prognostic biomarkers. This dissertation analyzed the expression of p53 and Ki67 as possible prognostic biomarkers in rectal cancer. An evaluation was done in untreated and residual tumor samples after RCT. The two cellular proteins p53 and Ki67 can be visualized using immunohistochemical staining techniques. The investigated samples derive from 225 patients with locally advanced rectal cancer (cUICC II/III). The obtained immunohistochemical data were correlated with the pathological data (for example TNM classification, tumor regression) and the follow-up-information of the patients. The results of these correlations show a constant pre- and post-therapeutic level of the tumorsupressor p53. Thus p53 expression level seems not be influenced by neoadjuvant RCT. In contrast Ki67 show a significant decreased expression level after neoadjuvant RCT (p<0,05). Probably, these elevated data predict a correlation between the grad of tumor regression and the Ki67 expression. Additionally this dissertation evaluated a digital image analysis system, which was also used for the analyses described previously. Immunohistochemistry is a well-established and widely used method in routine clinical diagnostics as well as in research. Standardization of staining procedures as well as criteria for analyses are still lacking and often requested for this method. Meanwhile, several computer-based evaluation systems are available. All samples were analysed conventionally as well as with the aid of the Ventana Image Analysis System (VIAS). The correlation of both datasets showed a strong correlation of both analysis systems, so the percentage of stained tumor cells, which was captured with both analysis measures showed a nearly linear correlation (correlation coefficient >0,9; p<0.00001).
Keywords: rectal cancer; p53; Ki67
Schlagwörter: p53; Ki67; Rektumkarzinom
 
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