CDH1 and neoplasm: Molecularly, the patterns of E-cadherin loss follow a classic Knudsen’s two-hit tumour suppressor hypothesis, involving CDH1 mutation (50–60% cases) [6], gene methylation (21–77% of cases) [7,8] and/or loss of heterozygosity in the region of 16q22.1 (or whole chromosomal arm) [2].