Prognostic significance of CD9 expression differs between tumour cells and stromal immune cells, and depends on the molecular subtype of the invasive breast carcinoma

Aims CD 9, a tetraspanin transmembrane protein, modulates cell motility, migration, and proliferation. The aim of this study was to investigate the prognostic significance of CD 9 expression in patients with invasive breast carcinoma ( IBC ). Methods and results CD 9 expression was evaluated in tissue microarrays of 1349 IBC samples via immunohistochemistry. CD 9 expression in tumour cells (T‐ CD 9 expression) and CD 9 expression in stromal immune cells (S‐ CD 9 expression) were analysed separately. T‐ CD 9 expression was observed in 732 (54.3%) cases, and was associated with lymph node metastasis, histological type, lymphovascular invasion, high histological grade, HER 2 positivity, a high Ki67 labelling index, and distant metastasis. S‐ CD 9 expression was observed in 833 (61.7%) cases, and was associated with large tumour size, histological type, high histological grade, negative hormone receptors, HER 2 positivity, a high Ki67 labelling index, and tumour‐infiltrating lymphocytes. Patients with T‐ CD 9 expression had shorter disease‐free survival ( DFS ) than those without T‐ CD 9 expression in the univariate and multivariate analyses. However, S‐ CD 9 expression correlated significantly with a favourable DFS in the univariate and multivariate analyses. In the subgroup analysis, T‐ CD 9 expression and S‐ CD 9 expression were independent markers for DFS in luminal A and luminal B ( HER 2‐negative) subgroups, respectively. Conclusions T‐ CD 9 expression could be a biomarker for poor prognosis in luminal A IBC , whereas S‐ CD 9 expression could be a marker of good prognosis in luminal B ( HER 2‐negative) IBC . Therefore, tumour compartment‐specific analyses considering molecular subtypes are necessary to study the prognostic significance of CD 9 expression in IBC .