Figure 4.

Hypermethylation of the G0S2 locus predicts rapid recurrence and death in an independent ACC cohort. A. Stratification of carcinomas from FMUSP+UM Primary ACC Cohort by grade (mitotic counts, where <20 mitotic counts/50 high-powered fields [HPF] is “low grade” and >20/50 HPF is “high grade”) identifies two subgroups of carcinomas with failure to achieve median DFS (low grade) and median DFS of 7.8 mo (high grade) following R0/RX resection. B. Stratification of primary ACC by measured or inferred G0S2 methylation status demonstrates that patients with G0S2 Methylated carcinomas have rapid recurrence and median DFS of 14 months following R0/RX resection. In contrast to patients with G0S2 Unmethylated carcinomas that fail to achieve median DFS, only 1 patient in the G0S2 Methylated group remains disease-free at >24 months, consistent with CIMP-high/G0S2 Methylated carcinomas from ACC-TCGA. C. Stratification of primary ACC by measured or inferred G0S2 methylation status demonstrates that patients with G0S2 Methylated carcinomas have dismal OS outcomes, with median OS of 17 months compared to failure to achieve median OS in the G0S2 Unmethylated group. D. G0S2 Methylated primary carcinomas were identified at statistically comparable frequency in patients with high grade disease (13/25) and in patients with low grade disease (13/44). E. G0S2 Methylated primary carcinomas were identified in patients with ENSAT II-IV disease at diagnosis without predilection for late stage disease.