Validation of tumor‐associated macrophage ferritin light chain as a prognostic biomarker in node‐negative breast cancer tumors: A multicentric 2004 national PHRC study

Novel prognostic biomarkers are imperatively needed to help direct treatment decisions by typing subgroups of node-negative breast cancer patients. Large screening of different biological compartments, such as the proteome, by means of high throughput techniques may greatly help scientists to find such markers. The present retrospective multicentric study included 268 node-negative breast cancer patients. We used a proteomic approach of SELDI-TOF-MS screening to identify differentially expressed cytosolic proteins with prognostic impact. The screening cohort was composed of 198 patients. Seventy supplementary patients were included for validation. Immunohistochemistry (IHC) and immunoassay (IA) were run to confirm the prognostic role of the marker identified by SELDI-TOF-MS screening. IHC was also used to explore links between selected marker and epithelial-mesenchymal transition (EMT)-like, proliferation and macrophage markers. Ferritin light chain (FTL) was identified as an independent prognostic marker (HR 5 1.30–95% CI: 1.10–1.50, p 5 0.001). Validation step by means of IHC and IA confirmed the prognostic value of FTL level. CD68 IHC showed that FTL was stored in tumor-associated macrophages (TAM), which exhibit an M2-like phenotype. We report here, first, the validation of FTL as a breast tumor prognostic biomarker in node-negative patients, and second, the fact that FTL is stored in TAM. Sporadic breast cancer is obviously a disease where further molecular characterization is needed to improve patients monitoring because patients with the same diagnosis can have markedly different clinical outcome. Approximately 70% of patients with node-negative breast cancer will be metastasis-free 10 years after initial treatment without adjuvant chemotherapy, whereas 30% will develop metastatic relapse (MR). Traditional prognostic markers and indexes are not sufficient for precise risk-group discrimination in breast cancer. Current guidelines, such as St Gallen or NIH ones,