Association of microsatellite instability with distinct clinical and molecular characteristics in resected colon cancer: Analysis of a platform trial of the AIO colorectal study group—Colopredict Plus.

Medientyp: E-Artikel

Titel: Association of microsatellite instability with distinct clinical and molecular characteristics in resected colon cancer: Analysis of a platform trial of the AIO colorectal study group—Colopredict Plus

Beteiligte: Reinacher-Schick, Anke C.; Juette, Hendrik; Noepel-Duennebacke, Stefanie; Arnold, Dirk; Basara, Nadezda; Boehner, Hinrich; Dahm, Thorsten; Feder, Inke Sabine; Hansen, Olaf; Hiller, Wolfgang; Leins, Alexander; Müller, Lothar; Ueberrueck, Torsten; Teschendorf, Christian; Trenn, Guido; Verdoodt, Berlinda; Zwingmann, Nadine; Uhl, Waldemar; Tannapfel, Andrea

Erschienen: American Society of Clinical Oncology (ASCO), 2017

Sprache: Englisch

DOI: 10.1200/jco.2017.35.15_suppl.e15086

ISSN: 0732-183X; 1527-7755

Schlagwörter: Cancer Research ; Oncology

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Beschreibung: e15086 Background: High microsatellite instability (MSI-H) is a prognostic marker in resected colon cancer (CC) identified in post-hoc analysis of multiple trials. However, validation in real-life cohorts and its association with clinical and molecular markers is lacking. Methods: In Sep 2013 we started a platform trial in 49 German cancer centers recruiting patients with UICC stage II and III CC diagnosed between 2008 to 2016. MSI was tested by immunohistochemistry (IHC) of mismatch repair proteins MLH1, MSH2, MSH6 and PMS2. In case of any loss of protein expression (IHC neg), fragment length analysis (FLA) was performed, defining MSI high tumors (MSI-H) and MS stable tumors (MSS). Besides, mutations in known prognostic factors for CC such as RAS, BRAF, PI3K and others were determined by next generation sequencing (NGS). Results: By end of 2016, 1249 patients have been recruited into the trial: median age 73yrs., stage II/III: 686/563 pts. So far, tissue was analysed in 512 pts. Of these, 182 pts. were IHC neg with 116 pts. tested MSI-H upon FLA (22.7%). Median age was 73yrs., female/male: 260/252 pts., stageII/III: 292/220 pts. Association of MS status with clinical factors is shown in Table 1. Upon NGS analysis we found 16.3% BRAF mutations, 39% KRAS mutations, 2.8% NRAS mutations and 22.6% PI3K mutations. MSI-H status was significantly associated with BRAF mutation and wildtype status of RAS. Conclusions: We found a higher percentage of MSI-H cancers in our registry compared to reported data from randomised trials, possibly related to a higher median age in this real-life cohort. MSI-H was associated with female sex, primary tumor site, and distinct molecular markers and should therefore be considered a heterogeneous subgroup of CC. Updated analysis including NGS data and survival will be presented at the meeting. Clinical trial information: AIO- KRK-0413, DKRS:00004305. [Table: see text]

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