High microsatellite instability (MSI-H) is a prognostic marker in early colon cancer (CC) identified in retrospective analysis of many trials. However, broad validation in real-life cohorts and its association with clinical and molecular markers is lacking.
In Sep 2013 the molecular registry trial Colopredict Plus was intiatied in 70 German community cancer centers recruiting patients with UICC stage II and III CC. MSI was tested by immunohistochemistry (IHC) of mismatch repair proteins MLH1, MSH2, MSH6 and PMS2. In case of any loss of protein expression fragment length analysis (FLA) was performed, defining MSI high tumors (MSI-H) and MS stable tumors (MSS). Moreover, mutations in known prognostic factors in CC such as RAS, BRAF, PI3K and others were determined by next generation sequencing (NGS).
By April 2018, 2102 patients have been recruited: median age 72 yrs., stage II/III: 1108/994 pts. So far, tissue was analysed in 1342 pts. Of these, 377 pts. were IHC neg with 290 pts. subsequently tested MSI-H upon FLA (21.6%). Median age was 73 yrs. female/male: 677/665 pts., stage II/III: 736/606 pts. Association of MS status with clinical and molecular factors is shown in the table. Upon NGS analysis we found 18.9% BRAF mutations, 41.5% KRAS mutations, 3.2% NRAS mutations and 25.1% PI3K mutations. MSI-H status was significantly associated with BRAF mutation and wildtype status of RAS.
MSI-H was more frequent in this community based registry compared to randomised trials, possibly related to a higher median age in our cohort. MSI-H was associated with female sex, right-sided primary tumor and BRAF mutations representing a heterogeneous subgroup of CC. First survival data will be presented at the meeting. Table: Association of clinical features with MSI-H in patients with CC (MS status determined by FLA).Table: 519P
|All||MSI-H (%)||MSS (%)|
|1342||290 (21,6)||1052 (78,4)|
|Male||677||78 (11,5)||599 (88,5)|
|Female||665||212 (31,9)||453 (68,1)|
|Stage II||736||181 (24,6)||555 (75,4)|
|Stage III||606||109 (18)||497 (82)|
|Right Colon||793||242 (30,5)||551 (69,5)|
|Left Colon||536||47 (8,8)||489 (91,2)|
Clinical trial identification
DRKS Registry number: DRKS00004305 Release Date: 09-JAN-2013.
Legal entity responsible for the study
Ruhr-University Bochum, Institute of Pathology; Department of Hematology, Oncology and Palliative Care, St. Josef-Hospital.
State of North-Rhine Westfalia, Roche Pharma GmbH.
A. Reinacher-Schick: Honoria: Amgen, Roche, Pfizer, Sanofi-Aventis, Merck-Serono, Shire, Calgene, Lilly, BMS; Advisory board member: Amgen, Roche, Pfizer, Sanofi-Aventis, Celgene, Lilly, BMS, Merck-Serono; Studies sponsored by: Roche, Sanofi-Aventis, Calgene, Ipsen. H. Juette: Honoria: Roche, MSD, BMS, AstraZeneca, Amgen. S. Noepel-Duennebacke: Advisory board member: Bexalta, BMS; Studies sponsored by: Roche, Sanofi-Aventis, Celgene, Ipsen. D. Arnold: Honoraria: Bayer, Biocompatibles, Lilly, Merck, MSD, Roche, Sanofi, Servier, Sirtex; Advisory board member: Bayer, Lilly, Merck, Roche, Sanofi, Servier, Sirtex, Termuno; Studies sponsored by: Mologen, Roche, Sanofi. C. Teschendorf: Advisory board member: Roche. A. Tannapfel: Honoraria: Amgen, Roche, Pfizer, Merck-Serono, Celgene, BMS; Advisory board member: Amgen, Roche, Pfizer, Sanofi-Aventis, Celgene, BMS, Merck-Serono; Studies sponsored by: Roche, Celgene, Ipsen. All other authors have declared no conflicts of interest.