Immunoglobulin free light chains are biomarkers of poor prognosis in basal-like breast cancer and are potential targets in tumor-associated inflammation

Inflammation is an important component of various cancers and its inflammatory cells and mediators have been shown to have prognostic potential. Tumor-infiltrating mast cells can promote tumor growth and angiogenesis, but the mechanism of mast cell activation is unclear. In earlier studies, we demonstrated that immunoglobulin free light chains (FLC) can trigger mast cells in an antigen-specific manner. Increased expression of FLC was observed within stroma of various human cancers including those of breast, colon, lung, pancreas, kidney and skin, and FLC expression co-localized with areas of mast cell infiltration. In a large cohort of breast cancer patients, FLC expression was shown associated with basal-like cancers with an aggressive phenotype. Moreover, lambda FLC was found expressed in areas of inflammatory infiltration and its expression was significantly associated with poor clinical outcome. Functional importance of FLCs was shown in a murine B16F10 melanoma model, where inhibition of FLC-mediated mast cell activation strongly reduced tumor growth. Collectively, this study identifies FLCs as a ligand in the pro-tumorigenic activation of mast cells. Blocking this pathway may open new avenues for the inhibition of tumor growth, while immunohistochemical staining of FLC may be helpful in the diagnosis and prognosis of cancer

Supplementary Material for: Nuclear Factor-κB Clinical Significance in Breast Cancer: An Immunohistochemical Study

Objectives: Nuclear factor κB (NF-κB) is a superfamily of transcription factors that plays a key role in cancer genesis and progression. The present study aimed to explore the exact role of NF-κB/p65 as a marker in breast cancer and its relationship with other prognostic markers, such as tumour grade, tumour size, hormone receptors, and HER-2 expression. Methods: Ninety-nine unselected formalin-fixed paraffin-embedded invasive ductal and lobular tissue sections were evaluated by immunohistochemistry methods to measure NF-κB/p65 expression, ER, PR, HER-2 and Ki-67. The correlation between NF-κB/p65 and clinicopathological parameters was assessed. Results: NF-κB/p65 was only found in the cytoplasm and positively correlated with large tumours (≥2 cm) and high-grade tumours (P< 0.001 and P= 0.018, respectively). Other breast cancer markers, such as histological type (P= 0.766), HER-2 (P= 0.416), PR (P= 0.356), and ER (P= 0.606), had no significant link with NF-B/p65 expression. Furthermore, no significant relation with the Ki-67 marker was detected (P= 0.117). Conclusion: The current study discovered a link between NF-κB/p65 overexpression and both large tumour size and higher grade. This might mean that the expression of NF-κB/p65 is associated with aggressive biological activity in breast cancer and that studying the mechanisms that lead to NF-κB/p65 cytoplasmic accumulation could lead to the discovery of novel therapeutic methods