A B S T R A C T PurposeAccurate assessments of recurrence risk and absolute treatment benefit are needed to inform colon cancer adjuvant therapy. The 12-gene Recurrence Score assay has been validated in patients with stage II colon cancer from the Cancer and Leukemia Group B 9581 and Quick and Simple and Reliable (QUASAR) trials. We conducted an independent, prospectively designed clinical validation study of Recurrence Score, with prespecified end points and analysis plan, in archival specimens from patients with stage II and III colon cancer randomly assigned to fluorouracil (FU) or FU plus oxaliplatin in National Surgical Adjuvant Breast and Bowel Project C-07. MethodsRecurrence Score was assessed in 892 fixed, paraffin-embedded tumor specimens (randomly selected 50% of patients with tissue). Data were analyzed by Cox regression adjusting for stage and treatment. ResultsContinuous Recurrence Score predicted recurrence (hazard ratio for a 25-unit increase in score, 1.96; 95% CI, 1.50 to 2.55; P Ͻ .001), as well as disease-free and overall survival (both P Ͻ .001). Recurrence Score predicted recurrence risk (P ϭ .001) after adjustment for stage, mismatch repair, nodes examined, grade, and treatment. Recurrence Score did not have significant interaction with stage (P ϭ .90) or age (P ϭ .76). Relative benefit of oxaliplatin was similar across the range of Recurrence Score (interaction P ϭ .48); accordingly, absolute benefit of oxaliplatin increased with higher scores, most notably in patients with stage II and IIIA/B disease. ConclusionThe 12-gene Recurrence Score predicts recurrence risk in stage II and stage III colon cancer and provides additional information beyond conventional clinical and pathologic factors. Incorporating Recurrence Score into the clinical context may better inform adjuvant therapy decisions in stage III as well as stage II colon cancer.

The 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.

In the largest single medical center series of renal transplant patients with SLE, recurrent LN was more common than reported in the literature, but was not always associated with allograft loss. Recurrent LN was often present in the absence of clinical and serologic evidence of active SLE.