Intratumoral desmoplastic stroma in carcinoma brain metastases harbors stromal cells with a cancer-associated fibroblast (CAF)-like immunophenotype.

Background

Research on the tumor microenvironment of brain metastases (BM) has largely focused on immune response, while the intratumoral stromal compartment remains poorly characterized. In primary carcinomas, cancer-associated fibroblast (CAF) are intratumoral stromal cells that enable tumor progression. A subset of carcinoma BM shows intratumoral desmoplastic stroma (IDS) including stromal cells. This raises the question of whether this represents a CAF population in an organ devoid of resident fibroblasts.

Methods

Whole-slide immunohistochemistry using a CAF marker panel (ASMA, CD90, COL11A1, SPARC) was performed in 19 carcinoma BM with IDS and in 10 glioblastomas. Stroma staining was scored semi-quantitatively (0-3). An independent cohort of 20 primary carcinomas with desmoplastic stroma was analyzed descriptively using the same approach.

Results

IDS stroma cells in BM exhibited consistent CAF-like immunophenotypes across the panel. Marker expression did not differ by primary tumor site (ASMA p = 0.439; CD90 p = 0.711; COL11A1 p = 0.328; SPARC p = 0.369). Compared with glioblastomas, carcinoma metastases showed markedly higher ASMA and COL11A1 scores ( p < 0.001 each). The summed CAF panel score was substantially higher in carcinoma metastases than in glioblastomas (p < 0.001). IDS cells lacked immunoreactivity supporting glial or endothelial origin (GFAP/S100/Olig2 negative; CD34 negative) and showed no evidence of entrapped axons.

Conclusion

A subset of carcinoma BM contains an IDS compartment with a CAF-like immunophenotype that is distinct from glioblastoma and normal brain. These findings provide a histopathological framework supporting the presence of an intratumoral stromal compartment with a CAF-like immunophenotype in BM and motivate mechanistic studies to define cellular origin, subtype composition, and functional roles.