Applikation der Comparativen Genomischen Hybridisierung (CGH) zur Vorhersage des Ansprechens von Rektumkarzinomen auf neoadjuvante Radiochemotherapie

Application of Comparative Genomic Hybridization (CGH) for response prediction of rectal adenocarcinoma to preoperative chemoradiotherapy

by Jaje Beckmann
Doctoral thesis
Date of Examination:2011-10-17
Date of issue:2011-10-12
Advisor:Dr. Marian Grade
Referee:Prof. Dr. Michael Ghadimi
Referee:Prof. Dr. Laszlo Füzesi
Persistent Address: http://hdl.handle.net/11858/00-1735-0000-0006-B27A-6

 

 

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Abstract

English

Introduction - Standard treatment of rectal cancer patients in UICC stages II and III comprises preoperative chemoradiotherapy followed by radical surgery. But there is a wide spectrum of tumor responsiveness, ranging from complete response to complete resistance. The aim of this study was to find predictive biomarkers, helpful for optimal individual therapy. Materials and Methods - Pre therapeutic biopsies of 42 patients, treated with 5-FU based preoperative chemoradiotherapy, because of locally advanced rectal cancer were analyzed by metaphase comparative genomic hybridization to prospectively identify genomic imbalances that might assist in stratifying tumors into responsive or non-responsive. Results Tumors were later divided into two Groups. 21 rectal cancers were classified as responsive, while 21 were non-responsive, based on T-Level-down-sizing. We could show that gains of chromosomal regions 7q32-q36 and 7q11-q31, and amplifications of 20q11-q13 were significantly associated with responsiveness to preoperative chemoradiotherapy (P<0.05). However, the probability to detect these copy number changes by chance is high (P=0.21). Conclusion - Pre-therapeutic evaluation of chromosomal copy number changes may be of value for response prediction of rectal cancers to preoperative chemoradiotherapy. Regarding our results we cannot reject the possibility that these three chromosomal aberrations were discovered by random chance. (P=0.21).
Keywords: rectum; carcinoma; therapy; chemoradiotherapy; preoperative; surgery; Comparative Genomic; Hybridisation; CGH; chromosomal imbalances;

Other Languages

Adenokarzinme des Rektums gehören zu den häufigsten Tumoren der westlichen Welt. In fortgeschrittenen Stadien (UICC II/III) ist die neoadjuvante Radiochomotherapie, gefolgt von radikaler Chirurgie Standard. Allerding reicht das Spektrum des Ansprechens von kompletter Remission bis kompletter Resistenz. Ziel dieser Arbeit war es daher auf chromosomaler Ebene Biomarker zur prätherapeutischen Einschätzung und Therapieplanung zu finden. Wir untersuchten 42 Patienten mit rektalen Karzinomen der UICC-Stadien II und III. Alle neoadjuvant auf Basis von 5-FU radiochemotherapiert. Jeweils 21 Responder und 21 Non-responder mittels Comparativer Genomischer Hybridisierung (CGH). Als Definition von Respons wählten wir die T-Level Reduktion. Der Vergleich der beiden Gruppen zeigte, dass Responder signifikant häufiger (p<0,05) Zugewinne der chromosomalen Regionen 7q32-q36, 7q11-7q31 und Amplifikationen der Region 20q11-20q13 aufweisen. Es ist allerdings (bei einem p-Wert von 0,21) vom aktuellen Standpunkt gesehen unsicher, ob diese genomischen Veränderungen tatsächlich biologische Unterschiede zwischen den beiden Gruppen charakterisieren oder lediglich Artefakte darstellen.
Schlagwörter: Rektumkarzinom; Darmkrebs; neoadjuvant; Radiochemotherapie; CGH; Comparative Genomische Hybridisierung; Response;
 
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