Neuroendocrine differentiation correlates with hormone receptor expression and decreased survival in patients with invasive breast carcinoma

Abstract

Invasive breast carcinoma (IBC) with neuroendocrine (NE) differentiation has been controversial in terms of its definition and clinical outcome. We investigated the incidence and clinical significance of NE differentiation in patients with IBC. We performed immunohistochemistry for NE markers, chromogranin-A and synaptophysin on 1428 IBC samples using tissue microarrays and classified cases with NE differentiation into two groups, focal (1-49% tumour cells positive for any NE marker) and diffuse (≥50% tumour cells positive) groups. Fifty-nine cases (4.1%) showed NE differentiation immunohistochemically, and the majority did not show typical NE morphology. The presence of NE differentiation showed a significant association with positive oestrogen receptor (P = 0.001) and progesterone receptor (P = 0.008) status. Patients with NE differentiation showed worse overall survival (OS) and disease-free survival (DFS) than those without NE differentiation in both univariate (P < 0.001 for both) and multivariate (OS, P = 0.004; DFS, P < 0.001) analyses. IBC with NE differentiation is a distinct subtype of mammary carcinoma with an aggressive clinical outcome.