Digital Whole Slide Image Analysis of Elevated Stromal Content and Extracellular Matrix
Protein Expression Predicts Adverse Prognosis in Triple-Negative Breast Cancer
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis
and limited treatment options. This study evaluates the prognostic value of stromal
markers in TNBC, focusing on the tumor–stroma ratio (TSR) and overall stroma ratio
(OSR) in whole slide images (WSI), as well as the expression of type-I collagen, type-III
collagen, and fibrillin-1 on tissue microarrays (TMAs), using both visual assessment
and digital image analysis (DIA). A total of 101 female TNBC patients, primarily treated
with surgery between 2005 and 2016, were included. We found that high visual OSR correlates
with worse overall survival (OS), advanced pN categories, lower stromal tumor-infiltrating
lymphocyte count (sTIL), lower mitotic index, and patient age (p < 0.05). TSR showed
significant connections to the pN category and mitotic index (p < 0.01). High expression
levels of type-I collagen (>45%), type-III collagen (>30%), and fibrillin-1 (>20%)
were linked to significantly worse OS (p = 0.004, p = 0.013, and p = 0.005, respectively)
and progression-free survival (PFS) (p = 0.028, p = 0.025, and p = 0.002, respectively),
validated at the mRNA level. Our results highlight the importance of stromal characteristics
in promoting tumor progression and metastasis and that targeting extracellular matrix
(ECM) components may offer novel therapeutic strategies. Furthermore, DIA can be more
accurate and objective in evaluating TSR, OSR, and immunodetected stromal markers
than traditional visual examination.