Clinical Experience with Mismatch Repair (MMR) Status and OncoType DX® Colon Cancer Recurrence Score® Assay in 917 Patients with Stage II Colon Cancer
Helen Bailey, Joseph Anderson, Vivian Tan, Athanasios C Tsiatis, Frederick L Baehner, June Liu, Margarita Lopatin, Mark Lee, Carl Millward. Genomic Health, Inc., Redwood City, CA; University of California, San Francisco, CA
Background: Standardized clinically-validated tools to quantify recurrence risk can improve adjuvant treatment decisions for colon cancer patients. MMR status by immunohistochemistry (MLH1 and MSH2) and Recurrence Score by quantitative RT-PCR have been validated as independent predictors of colon cancer recurrence risk in QUASAR (J Clin Oncol, 10;29(35):4611-9, 2011), CALGB 9581 (J Clin Oncol, 29(Supp): Abstract 3518, 2011), and NSABP C-07 (O'Connell, ASCO Annual Meeting, 2012). Here we report our experience for stage II colon cancer patients who obtained MMR status and Recurrence Score values from the Genomic Health Clinical Laboratory.
Design: MMR status was determined using immunohistochemistry (IHC) assays for MLH1 and MSH2 (validated in 170 colon cancer specimens by comparing to assessments from the CAP/CLIA-certified reference laboratory (Vitro, Miami, FL) used in the QUASAR clinical validation study, with a concordance rate of 99.2% (95% CI 95.8–99.9%) for MMR). Standardized quantitative RT-PCR analysis for the 12 genes was performed on 30 μm manually-microdissected fixed primary tumor tissue. Recurrence Score values were calculated according to the pre-specified algorithm.
Results: Between Jan and Sept 2012, MMR status was assessed for 917 patients (51% female, 40% ≥70 years old, 10% with mucinous carcinoma). 197 (21%) were MMR-deficient (MMR-D) and 720 (79%) were MMR-proficient (MMR-P). As expected, among the MMR-D tumors, loss of MLH1 expression by IHC was more common (87%) than loss of MSH2 expression (13%). Patients with MMR-D tumors were more likely to have mucinous histology (19% vs 8%), older age (54% vs 36% with age ≥ 70) and to be female (61% vs 49%), all p<0.01. Recurrence Score results were available for 665 MMR-P patients for whom both MMR and the Recurrence Score were ordered. Scores spanned a wide range from 0 to 67, with a median of 26 and an interquartile range of 19-34. No significant differences were observed by gender or age.
Conclusions: The Genomic Health Clinical Laboratory MMR IHC Assay has been rigorously validated, and further studied in a large cohort of contemporary stage II colon cancer patients. Stage II colon cancer patients with MMR-P tumors represent a heterogeneous population with a wide range of colon cancer biology as revealed by the Recurrence Score result.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 98, Wednesday Morning