3526: Proximal and distal colon tumors as distinct biologic entities with different prognoses.

Details

Serval ID
serval:BIB_74F86B683886
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
3526: Proximal and distal colon tumors as distinct biologic entities with different prognoses.
Title of the conference
Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
Author(s)
Missiaglia E., Jacobs B., Di Narzo AF, Soneson C., Roth A., Bosman F., D'Ario G., Klingbiel D., Yan P., Delorenzi M., Tejpar S.
Address
Chicago, USA, May 31 - June 04, 2013
ISBN
0732-183X
ISSN-L
0732-183X
Publication state
Published
Issued date
2013
Volume
31
Series
Journal of Clinical Oncology
Pages
3526
Language
english
Abstract
Background: It has been shown that tumors arising in the proximal and distal colon, defined by the embryological midgut and hindgut, have distinctive clinical and molecular features, but very little is known concerning the differences in the mechanism of tumorigenesis and the effect that this could have on therapy. Methods: The distribution of clinico-pathological and molecular features was evaluated between proximal (N = 1110, Caecum to hepatic flexure) and distal colon (N = 1728, splenic flexure down to sigmoid) in patients included in the PETACC3 trial. Gene expression profile was also available from 783 tumors and 32 normal colon. A further set of 473 metastatic patients treated with cetuximab combined with chemotherapy (De Roock Lancet Oncol. 2010) was used to test tumor location with response. Results: Pathological features, such as tumor differentiation, and mucinous histology as well as molecular characteristics, such as MSI status, BRAF, PIK3Ca mutations and LOH18q loss show higher frequency in proximal compared to distal colon (N = 1214; Fisher test, P<0.001). Proximal tumors showed a significantly worse overall survival (N= 2838; HR=1.4 [1.18 - 1.64] P<0.001) and survival after relapse (N = 861; HR=1.97 [1.65 - 2.35] P <0.001) only if they were stage III at diagnosis, while no difference was observed for relapse free survival. Microarray profiling identified 997 genes differentially expressed between the two anatomical sites, after adjustment for age, gender, mucinous histology, BRAF, KRAS and MSI status. Only 20 of those were present in normal colon site comparison indicating tumor specificity. Data mining analysis of the differentially expressed genes showed that the distal colon is characterized by an enrichment for MAPK activated pathways as well as for the cetuximab response gene signature (Khambata-Ford JCO 2007). In fact, cetuximab treated KRAS/BRAF wild-type tumors in distal colon had prolonged PFS and a 2-fold higher response rate then proximal. Conclusions: Proximal and distal colon tumors have distinctive patterns of clinical-pathological and molecular features. These biological differences likely have significant prognostic and therapeutic implications.
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10/08/2016 9:10
Last modification date
20/08/2019 14:32
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