PIK3CA and extramammary Paget disease: Furthermore, DNA sequence analysis of EMPD revealed that 19% of cases had mutant RAS or RAF genes and 35% of cases had mutations in PIK3CA, which encodes the catalytic subunit of PI3K, or in AKT1 that activates these pathways, suggesting that these two signaling pathways play critical roles in the pathogenesis of EMPD (64).