Biologic Determinants of Tumor Recurrence in Stage II Colon Cancer: Validation Study of the 12-Gene Recurrence Score in Cancer and Leukemia Group B (CALGB) 9581
Biologic Determinants of Tumor Recurrence in Stage II Colon Cancer: Validation Study of the 12-Gene Recurrence Score in Cancer and Leukemia Group B (CALGB) 9581
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DOI：
10.1200/jco.2012.45.1096
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发表时间：
2013-05-10
影响因子：
45.3
通讯作者：
Bertagnolli, Monica M.
中科院分区：
文献类型：
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作者：
Venook, Alan P.;Niedzwiecki, Donna;Bertagnolli, Monica M.
目的加深对肿瘤复发生物学的了解，提高辅助治疗的决策水平。我们对癌症和白血病B组（CALGB） 9581患者的肿瘤标本进行了12基因复发评分（RS）的验证研究，RS是一种整合基质反应和细胞周期基因表达的定量分析。scalgb 9581随机将1713例II期结肠癌患者分为依来科单抗治疗组和观察组，未发现生存期差异。本文报道的分析包括所有有可用组织和复发的患者（n = 162）和随机（约1:3）选择的非复发患者。采用预先指定的基因和先前验证的算法，采用定量逆转录酶聚合酶链反应对690份福尔马林固定石蜡包埋肿瘤样本进行RS评估。采用加权Cox比例风险回归分析RS与复发的相关性。结果持续RS与复发风险显著相关（P = 0.013），错配修复（MMR）基因缺陷与复发风险显著相关（P = 0.044）。在多变量分析中，RS是最强的复发预测因子（P = 0.004），与T分期、MMR、检查的淋巴结数量、分级和淋巴血管浸润无关。在T3 mmr完整（MMR-I）患者中，预先指定的低RS组和高RS组的5年平均复发风险分别为13% （95% CI， 10%至16%）和21% （95% CI， 16%至26%）。结论12基因RS可预测calgb9581ⅱ期结肠癌的复发。这与基质反应和细胞周期基因表达在结肠肿瘤复发中的重要性是一致的。RS似乎对T3 mmr - 1型肿瘤患者最具辨识力，尽管分级和淋巴血管侵袭等标志物在这类患者中没有增加价值。(C)美国临床肿瘤学会2013
PurposeA greater understanding of the biology of tumor recurrence should improve adjuvant treatment decision making. We conducted a validation study of the 12-gene recurrence score (RS), a quantitative assay integrating stromal response and cell cycle gene expression, in tumor specimens from patients enrolled onto Cancer and Leukemia Group B (CALGB) 9581.Patients and MethodsCALGB 9581 randomly assigned 1,713 patients with stage II colon cancer to treatment with edrecolomab or observation and found no survival difference. The analysis reported here included all patients with available tissue and recurrence (n = 162) and a random (approximately 1: 3) selection of nonrecurring patients. RS was assessed in 690 formalin-fixed paraffin-embedded tumor samples with quantitative reverse transcriptase polymerase chain reaction by using prespecified genes and a previously validated algorithm. Association of RS and recurrence was analyzed by weighted Cox proportional hazards regression.ResultsContinuous RS was significantly associated with risk of recurrence (P = .013) as was mismatch repair (MMR) gene deficiency (P = .044). In multivariate analyses, RS was the strongest predictor of recurrence (P = .004), independent of T stage, MMR, number of nodes examined, grade, and lymphovascular invasion. In T3 MMR-intact (MMR-I) patients, prespecified low and high RS groups had average 5-year recurrence risks of 13% (95% CI, 10% to 16%) and 21% (95% CI, 16% to 26%), respectively.ConclusionThe 12-gene RS predicts recurrence in stage II colon cancer in CALGB 9581. This is consistent with the importance of stromal response and cell cycle gene expression in colon tumor recurrence. RS appears to be most discerning for patients with T3 MMR-I tumors, although markers such as grade and lymphovascular invasion did not add value in this subset of patients. (C) 2013 by American Society of Clinical Oncology