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Triple-negative breast cancer's (TNBC) adverse prognosis necessitates enhanced therapeutic strategies. The recognized molecular classifications, illustrate its heterogeneity yet omit spatial analysis and remain non-integrative in clinical protocols. This study intends to assess TNBC biomarker expression through immunohistochemistry (IHC) and correlate it with spatial gene expression profiles derived from spatial transcriptomics (ST). We examined a retrospective cohort of patients (pts) at Institut Jules Bordet, Belgium, undergoing primary surgery for early TNBC. ST (Visium® Spatial Gene Expression, 10X Genomics) on fresh frozen samples yielded spatial gene expression from tumor, stroma, and structures. Duplex IHC for Trop-2/AR and HER2/Ki-67 was done on serial sections, scored by H-score (Trop-2), Allred (AR), and guidelines (Ki67/HER2), adding ultra-low and null HER2. Analysis included descriptive stats, Spearman's for IHC-ST correlation, Mann-Whitney for gene expression, and Kaplan-Meier with log-rank for survival. Among the 92 pts included, Trop-2 IHC expression was high in 67% of pts, correlated with AR by IHC (r=0.3, p=0.004) and anti-correlated with Ki67 (r=-0.34). IHC expression correlated well with tumor-derived gene expression (r=0.54) and was inversely associated with prognosis (p=0.021). AR expression was scored both in tumor and stromal cells and was correlated (r=0.46) and also correlated with the respective gene expression (r=0.68). Stromal but not tumor AR was correlated with TILs (r=0.26, p=0.014), while only tumor AR correlated weakly with Ki67 (r=-0.21, p=0.04). Neither of the two was associated with prognosis. Importantly, using AR and Ki67 expression levels by IHC, we could construct a classifier that accurately identified LAR tumors, with a PPV of 93% and an NPV of 96%. HER2 by IHC was scored 2+, 1+, ultra-low, and null in 4.3%, 27.2%, 30.4%, and 38% of pts, respectively. Importantly, ERBB2 tumor gene expression in HER2 ultra-low tumors was significantly different compared to HER2 null tumors (p<0.0001), but similar to HER2 1+ tumors (p=0.49). Converting higher into lower resolution data might be feasible and pave the path for tailored therapies in TNBC.
Carausu et al. (Wed,) studied this question.