Do signal transduction cascades influence survival in triple-negative breast cancer? A preliminary study

Abstract

Background: Triple-negative breast cancer (TNBC) is a rather aggressive form of breast cancer, comprised by early metastasis formation and reduced overall survival of the affected patients. Steroid hormone receptors and the human epidermal growth factor receptor 2 are not overexpressed, limiting therapeutic options. Therefore, new treatment options have to be investigated. The aim of our preliminary study was to detect coherences between some molecules of intracellular signal transduction pathways and survival of patients with TNBC, in order to obtain some hints for new therapeutical solutions.

Methods: Thirty-one paraffin-embedded tumor tissue samples, which were determined to be negative for steroid hormone receptors as well as human epidermal growth factor receptor 2, were immunohistochemically stained for a number of signal transduction molecules from several signaling pathways. β-Catenin, HIF1α, MCL, Notch1, LRP6, XBP1, and FOXP3 were stained with specific antibodies, and their staining was correlated with patient survival by Kaplan-Meier analyses.

Results: Only two of the investigated molecules have shown correlation with overall survival. Cytoplasmic staining of HIF1α and centro-tumoral lymphocyte FOXP3 staining showed statistically significant correlations with survival.

Conclusion: The coherence of signal transduction molecules with survival of patients with TNBC is still controversially discussed in the literature. Our study comprises one more mosaic stone in the elucidation of these intracellular processes and their influences on patient outcome. Lots of research still has to be done in this field, but it would be worthwhile as it may offer new therapeutic targets for a group of patients with breast cancer, which is still hard to treat.

Keywords: Kaplan–Meier analysis; immunohistochemistry; signal transduction cascades.

Figure 1

Staining of triple-negative breast cancer tissue with antibodies against molecules of different signal transduction cascades. Notes: Blue: nuclear counterstain by hemalaun; brown: ABC staining of the respective signal transduction molecule. Magnification is 25 times. Abbreviation: ABC, Avidin-Biotin Complex.

Figure 2

Kaplan–Meier survival curves in correlation to staining intensity. Notes: Weak staining of the respective signal transduction molecule was compared to strong staining in respect to overall survival. If a staining was regarded as low or strong was determined with the median of Immune Reactive Score values. CT stands for centro-tumoral, meaning that lymphocytes in the center of the tumor are stained; Tum stands for a staining of tumor cells themselves. The P-value calculated from the log-rank test shows the statistical relevance. The survival curves of low and strong staining are different if P≤0.05. Abbreviations: N, nuclear staining; C, cytoplasmic staining; TLS, tumor-infiltrating lymphocytes.

Figure 2

Kaplan–Meier survival curves in correlation to staining intensity. Notes: Weak staining of the respective signal transduction molecule was compared to strong staining in respect to overall survival. If a staining was regarded as low or strong was determined with the median of Immune Reactive Score values. CT stands for centro-tumoral, meaning that lymphocytes in the center of the tumor are stained; Tum stands for a staining of tumor cells themselves. The P-value calculated from the log-rank test shows the statistical relevance. The survival curves of low and strong staining are different if P≤0.05. Abbreviations: N, nuclear staining; C, cytoplasmic staining; TLS, tumor-infiltrating lymphocytes.