HOXA9 and neoplasm: However, a difference in the frequency of methylation was apparent between the low/intermediate- and HG-NMIBC cohorts for HOXA9 and ISL1 genes: although the methylation frequency of the HOXA9 promoter in low/intermediate-grade tumours was similar to that previously described in the literature [12,13], it was found at markedly lower frequency in HG-NMIBC.