Paradoxical cadherin-catenin immunostaining in a case of invasive mammary carcinoma with ductal and lobular differentiation: A molecular correlation

We present a 66-year-old woman with right breast invasive mammary carcinoma with distinct areas consisting of lobular and tubular morphology. The areas with lobular morphology paradoxically demonstrated intact membranous expression of E-cadherin, membranous p120 expression, with loss of beta-catenin. In this lobular appearing area of tumor, massive parallel sequencing identified a p. Y835* (c.2504_2505del) variant in the CDH1 gene, which results in premature termination in the last exon and a truncated protein. The areas with tubular morphology unexpectedly demonstrated lack of E-cadherin and beta-catenin expression along with cytoplasmic p120 expression. In this tubular appearing area of tumor, massive parallel sequencing identified a variant in CDH1 at the exon–intron boundary (c.1711 G > A). Proposed mechanisms for absence of E-cadherin protein in this area include aberrant mRNA splicing or protein misfolding resulting from the missense alteration. Nevertheless, a genetic and phenotypic correlation in both morphologically distinct areas of the tumor is evident.