Abstract 5274: MSI, 18q LOH, and clinicopathological features in stage II sporadic colon cancers: Biomarker study in a phase III study of postoperative adjuvant chemotherapy for stage II colon cancer (SACURA trial)
Authors: Ishikawa Toshiaki , Uetake Hiroyuki , Ishiguro Megumi , Murotani Kenta , Ueno Hideki , Matsui Shigeyuki , Sugihara Kenichi , Tomita Naohiro ,   SACURA study group
Published: August 2015

Background and Purpose: SACURA trial is a multicenter, randomized phase III study which aims to evaluate the superiority of adjuvant treatment with UFT to observation only after surgery for stage II colon cancer. In an additional translational study, the mRNA expression of 5-FU-related enzymes, MSI and 18q LOH, and histopathological factors including budding are assessed to evaluate correlations with recurrences and survivals. Survival data will be open in 2016. In the present study, we investigated the correlations between clinicopathological features and the status of MSI and 18q LOH to reveal the characteristics of colon cancer in Japan.

Material and Methods: From 1038 of 2024 patients enrolled from October 2006 to July 2010, formalin-fixed, paraffin-embedded samples of resected tumors were obtained under informed consent. MSI was evaluated using 5 markers, BAT25, BAT26, D2S123, D5S346, and D17S250 selected from the international guidelines suggested by the National Cancer Institute collaborative meeting. MSI high (MSI-H) was defined as the presence of instability in more than 20% of the markers. Microsatellite stability (MSS) was defined as no unstable marker. 18qLOH was evaluated by 3 markers, D18S69, D18S74E, and D18S851. 18qLOH positivity was defined as the presence of LOH in any of the 18q markers. 18q LOH negativity was strictly defined as the presence of at least two informative markers and the absence of LOH. Each marker were amplified by PCR using fluorescence-labeled primers and analyzed on ABI 3130 Genetic Analyzer using GeneMapper Software Ver. 3.0.

Results: Among 1038 tumors, MSI-H was observed in 75 tumors (7.2%). MSI-L and MSS were observed in 24 (2.3%) and 936 tumors (90.5%), respectively. MSI-H was more frequent in female (p = 0.001), right-sided colon cancers (p 5cm tumors (p&lt; 0.0001), poorly-differentiated or mucinous cancers (p&lt; 0.0001), and abnormal CEA (p = 0.004). Age and Depth of tumor invasion had no correlation with MSI status. The 18q LOH phenotype was present in 531 tumors (51.2%) and LOH negativity was observed in 360 (34.7%). Informative LOH data was not available in 147 tumors (14.2%).Tumors with 18q LOH was more frequent in left -sided colon cancers(p&lt; 0.0001) and well to moderately-differentiated cancers (p = 0.008). Age, gender, the tumor size, depth of tumor invasion, and CEA had no correlation with 18q LOH status.

Conclusions: This is the first analysis for the status of MSI and 18q LOH in a large population of Japanese colon cancer patients from phase III study. Although the frequency of the MSI phenotype in this study was lower than those in the previous reports from western countries, clinicopathological characteristics of the tumors with MSI and 18q LOH were similar. Our future study in SACURA trial will contribute to establish the prognostic and/or predictive biomarkers in stage II colon cancer.

Citation Format: Toshiaki Ishikawa, Hiroyuki Uetake, Megumi Ishiguro, Kenta Murotani, Hideki Ueno, Shigeyuki Matsui, Kenichi Sugihara, Naohiro Tomita, SACURA study group. MSI, 18q LOH, and clinicopathological features in stage II sporadic colon cancers: Biomarker study in a phase III study of postoperative adjuvant chemotherapy for stage II colon cancer (SACURA trial). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5274. doi:10.1158/1538-7445.AM2015-5274