Fig. 3

Multistep model of evolution of tumours with morphological features indicative of mixed ductal and lobular carcinomas. a Co-existing lesions with both ‘ductal’ and ‘lobular’ morphology are frequently clonally related, suggesting shared origins of a common neoplastic clone. Early divergence leads to the co-occurrence of LCIS and DCIS, and in such cases LCIS and associated ILC are likely to be negative for E-cadherin. Tumour cells exhibiting a lobular pattern of growth can also emerge from the ‘ductal’ pathway, and in such cases E-cadherin might be positive or aberrantly expressed. Modified from McCart Reed et al. [58]. Immunohistochemical staining for E-cadherin in different tumours: b × 10 magnification showing co-existing E-cadherin-positive DCIS and E-cadherin-negative LCIS; c showing strong membrane E-cadherin positivity in tumour cell nests and aberrant (cytoplasmic) E-cadherin staining in adjacent single cells. DCIS, ductal carcinoma in situ; LCIS, lobular carcinoma in situ; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; - E-cad, E-cadherin loss; -/+ E-cad, variable expression (loss, positive, aberrant)