Abstract: Objective To explore the relationship between a proliferation-inducing ligand (APRIL) expression in primary tumor
foci of breast cancer and the patients’ prognosis. Methods Paraffin sections of surgical specimens were retrospectively
collected from 130 stage I-III breast cancer patients who received surgery between January 2000 and December 2002 in our
hospital. Immunohistochemistry was used to assess APRIL expression intensity in the tumor cells and density of interstitial
APRIL-positive cells, and their association was analyzed with the density of interstitial CD4 + and CD8 + cells and with the
histopathologic features, overall survival (OS), and disease-free survival (DFS) of the patients. Results APRIL positive staining
was found in the cytoplasm of the tumor cells, interstitial cells, and the extracellular matrix. APRIL intensity in the tumor cells
was positively correlated with the density of interstitial APRIL-positive cells (P=0.009) and Ki67 (P=0.003). The density of
interstitial APRIL-positive cells was positively correlated with the density of interstitial CD4+ cells (P<0.001) and CD8+ cells (P<
0.001). In hormone receptor negative patients (ER- and PR-), multivariate COX regression identified the density of interstitial
APRIL-positive cells as a positive prognostic factor for DFS (HR=0.313, 95% CI=0.107-0.920, P=0.035). Conclusions APRIL is
widely expressed in the interstitial immune cells in breast cancer. APRIL staining intensity in the tumor cells is positively
correlated with tumor proliferation, indicating that the immune cells might promote tumor proliferation by secreting APRIL. A
greater density of interstitial APRIL-positive cells is associated with a good prognosis in hormone receptor-negative patients.