Cohen Stacey A, Yu Ming, Baker Kelsey, Redman Mary, Wu Chen, Heinzerling Tai J, Wirtz Ralph M, Charalambous Elpida, Pentheroudakis George, Kotoula Vassiliki, Kalogeras Konstantine T, Fountzilas George, Grady William M
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 USA.
Division of Oncology, University of Washington, Seattle, WA USA.
Clin Epigenetics. 2017 May 2;9:46. doi: 10.1186/s13148-017-0347-1. eCollection 2017.
The CpG island methylator phenotype (CIMP) in stage III colon cancer (CRC) has been associated with improved survival after treatment with adjuvant irinotecan-based chemotherapy. In this analysis, we determine whether CIMP status in the primary CRC is concordant with the CIMP status of matched metastases in order to determine if assessment of CIMP status in the primary tumor can be used to predict CIMP status of metastatic disease, which is relevant for patient management as well as for understanding the biology of CIMP CRCs.
We assessed the CIMP status of 70 pairs of primary CRC and matched metastases using a CRC-specific panel of five markers (, , , , and ) where CIMP positive was defined as 3/5 positive markers at a percent methylated reference threshold of ≥10%. Concordance was compared using the Fisher's exact test and < 0.05 was considered significant.
Sixty-nine of the pairs (98.6%) showed concordant CIMP status in the primary tumor and matched metastasis; five (7.0%) of the pairs were concordantly CIMP positive. Only one pair (1.4%) had divergent CIMP status, demonstrating CIMP positivity (4/5 markers positive) in the primary tumor, while the matched metastasis was CIMP negative (0 markers positive).
CIMP status is generally concordant between primary CRCs and matched metastases. Thus, CIMP status in the primary tumor is maintained in matched metastases and can be used to inform CIMP-based therapy options for the metastases.
III期结肠癌（CRC）中的CpG岛甲基化表型（CIMP）与基于伊立替康的辅助化疗治疗后的生存改善相关。在本分析中，我们确定原发性CRC中的CIMP状态是否与匹配转移灶的CIMP状态一致，以确定原发性肿瘤中CIMP状态的评估是否可用于预测转移性疾病的CIMP状态，这与患者管理以及理解CIMP CRCs的生物学特性相关。
我们使用由五个标志物（、、、和）组成的CRC特异性检测组评估了70对原发性CRC及其匹配转移灶的CIMP状态，其中CIMP阳性定义为在甲基化百分比参考阈值≥10%时5个标志物中有3个阳性。使用Fisher精确检验比较一致性，P < 0.05被认为具有统计学意义。
69对（98.6%）在原发性肿瘤和匹配转移灶中显示出一致的CIMP状态；其中5对（7.0%）一致为CIMP阳性。只有1对（1.4%）具有不同的CIMP状态，原发性肿瘤显示CIMP阳性（4/5个标志物阳性），而匹配转移灶为CIMP阴性（0个标志物阳性）。
原发性CRC与其匹配转移灶之间的CIMP状态通常是一致的。因此，原发性肿瘤中的CIMP状态在匹配转移灶中得以维持，可用于为转移灶的基于CIMP的治疗方案提供参考。
