Immunophenotypic profile of tumor buds in breast cancer

Background: Tumor buds are associated with lympho-vascular invasion and lymph node metastases leading to the assumption that they are involved in the early metastatic process. Hence, it would be important to know if tumor buds can be targeted with the most widely used targeted therapies in breast cancer (BC) and if changes in hormone and Her2 status occur. The aim of this study was to answer these questions by determining whether hormone receptor (HR) and Her2 status are expressed in the tumor buds of a large cohort of BCs. Design: We constructed a tumor bud next-generation tissue microarray (ngTMA) consisting of n = 199 BCs of non-special type. Generally, two 1 mm punches were taken from the tumor bud areas in the periphery (PTB) and within the tumor center (ITB). HR and Her2 status was assessed using immunohistochemistry and fluorescence in situ hybridization, respectively. HR status was positive if 1% of tumor bud cells were positive. Her2 status was considered positive if bud cells showed strong complete membranous Her2 over-expression or Her2 amplification. Results: Most tumor buds were positive for estrogen (ER) (PTB: 86%; ITB: 88.3) and progesterone receptor (PgR) (PTB: 72%; ITB: 72.8%) and Her2 was positive in: PTB 11.5% and ITB 11%. A difference between the main tumor mass and tumor buds (PTB and ITB) was seen for PgR in 3.5% of cases (n = 7). No differences were seen for ER and Her2 between tumor buds and main tumor mass. Conclusion: Most tumor buds (96.5%) share the same HR and Her2 expression profile of the main tumor mass, implying that tumor buds relay on the same pathways as the main tumor mass and might be equally responsive to targeted therapies.