Inside the Tumor: Decoding the Feline Mammary Tumor Microenvironment and Its Prognostic Value—A Review
Abstract
Simple Summary
Abstract
1. Introduction
2. Tumor Necrosis
3. Tumor Angiogenesis
4. Tumor Fibrosis
5. Adipose Tissue
6. Tumor-Associated Inflammation
6.1. Tumor-Infiltrating Lymphocytes
6.2. Tumor-Infiltrating Macrophages
6.3. Other Immune Cells
6.4. Immune Phenotypes
6.5. Immune Checkpoints
7. Extracellular Vesicles
8. Epithelial–Mesenchymal Transition
9. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Marker (Technique) | Categories/Thresholds | Significance | Outcome | Statistical Model | Reference |
---|---|---|---|---|---|
Tumor necrosis | |||||
Necrosis (HE) | Absence, some necrosis, ≈30%, 60%, ≥90% | Yes | OS | MV | [39] |
25% cutoff | Yes | 1-year OS | UV | [27] | |
Absent, isolated cells, extensive | No | TSS/DFI | UV | [38] | |
25% cutoff | No | TSS | UV | [37] | |
Central necrosis of any type: present, absent | No | OS/TSS | UV | [28] | |
Ischemic central necrosis: present, absent | No | OS/TSS/DFI | UV | [35] | |
Comedo necrosis: present, absent Random necrosis: present, absent 25% cutoff | No | OS/TSS/DFI | UV | ||
Necrosis (HE stereology) | 0.130 cutoff | No | OS/TSS/DFI | UV | |
HIF-1α (IHC) | Overexpression: nuclear immunoreactivity in any tumor cells | Yes | 1-year OS | UV | [27] |
Tumor angiogenesis | |||||
VEGF (IHC) | 72.1% cutoff | Yes | OS | UV | [44] |
Score 0 (absence of staining), score 1 (weak immunoreactivity in <50% of tumor cells), score 2 (weak immunoreactivity in ≥50% or strong immunoreactivity in <50% of tumor cells), score 3 (strong immunoreactivity in ≥50% of tumor cells) Overexpression: scores 2 and 3 | No | TSS | UV | [45] | |
No | 1-year OS | UV | [27] | ||
MVD (IHC) | 29.5 cutoff | No | OS | UV | [44] |
Tumor fibrosis | |||||
Collagen fibers (SHG) * | Collagen density (mean cutoff) | Yes | OS/DFI | UV | [46] |
Tumor-stroma boundary: N (not enough collagen to score), score 0 (distinct division), score 1 (discrete) Tumor-stroma boundary (mean cutoff) | Yes | OS/DFI | UV | ||
Yes | OS/DFI | MV | |||
Collagen fiber number (mean cutoff) | No | OS/DFI | UV | ||
Yes | OS/DFI | MV | |||
Collagen fiber length (mean cutoff) | Yes | OS/DFI | UV | ||
Collagen fiber width (mean cutoff) | Yes | OS/DFI | UV | ||
Yes | DFI | MV | |||
Collagen fiber straightness (mean cutoff) | Yes | OS/DFI | UV | ||
Yes | DFI | MV | |||
Stromal response (HE) | None to mild, peritumoral, intratumoral | Yes | 1-year OS | UV | [27] |
α-SMA (IHC) | Immunoreactivity percentage: score 0 (absence of staining), score 1 (1–10% positive CAFs), score 2 (11–50% positive CAFs), score 3 (51–80% positive CAFs), score 4 (81–100% positive CAFs) Immunoreactivity intensity: score 0 (no staining), score 1 (weak), score 2 (moderate), score 3 (intense/strong) Final score = percentage score + intensity score Low immunoreactivity: final score < 6; high immunoreactivity: final score ≥ 6 | Yes | TSS/DFI | UV | [47] |
Adipose tissue | |||||
Leptin (ELISA) | 4.17 pg/mL cutoff | Yes | DFI | UV | [32] |
n | Categories | % of Cases | Survival Times (Median) | Significance | Survival Variable | Statistical Model | Reference | |
---|---|---|---|---|---|---|---|---|
170 | Lymphocytes and plasma cells | - | - | No | - | - | [106] | |
202 | Quantity of acute and chronic cellular inflammation | - | - | Yes | OS | UV | [39] | |
No | OS | MV | ||||||
24 | Absent to negligible | 37.5% | - | - | - | - | [15] | |
Few moderate peritumoral lymphoid aggregates | 41.7% | - | - | - | - | |||
Moderate peritumoral lymphoid aggregates | 20.8% | - | - | - | - | |||
108 | Absent or mild | 31.5% | 18 months | No | TSS | UV | [37] | |
Lymphoplasmacytic | 54.6% | 15 months | ||||||
Neutrophilic or pleocellular | 13.9% | 9 months | ||||||
342 | Mononuclear | Absent to mild | 48.5% | 13.2 months | Yes | OS/TSS | UV | [28] |
Moderate to severe | 51.4% | 8.5 months | ||||||
180 | Mononuclear | Absent to mild | 42.8% | - | - | - | - | [108] |
Moderate to severe | 57.2% | |||||||
395 | Absent to mild (mononuclear) | 52.7% | - | Yes | DFI/OS/TSS | UV | [107] | |
Moderate to severe (mononuclear) | 47.3% | TSS | MV | |||||
180 | Intratumoral Tregs (≥2 vs. <2/mm2) | 82.2% | - | Yes | DFI/OS/TSS | MV | [110] | |
Stromal Tregs (≥6 vs. <6/mm2) | 91.7% | DFI/OS/TSS | MV | |||||
Peritumoral Tregs (≥575 vs. <575/mm2) | 97.2% | DFI/OS/TSS | UV/MV | |||||
10 | Peripheral lymphocytes | 80.0% | - | - | - | - | [111] | |
49 | Positive score interstitial FoxP3+ lymphocytes | 71.4% | - | - | - | - | [112] | |
None seen | 14.3% | - | - | - | - | |||
<1% of FoxP3+ interstitial lymphocytes | 8.2% | - | - | - | - | |||
1–5% of FoxP3+ interstitial lymphocytes | 42.9% | - | - | - | - | |||
6–30% of FoxP3+ interstitial lymphocytes | 26.5% | - | - | - | - | |||
>30% of FoxP3+ interstitial lymphocytes | 8.2% | - | - | - | - | |||
40 | Lymphocytic infiltration (yes vs. no) | 67.5% | - | - | - | - | [31] | |
56 | Lymphocytic infiltration (yes vs. no) | 66.1% | - | - | - | - | [32] | |
73 | Lymphocytic infiltration (yes vs. no) | 78.1% | - | - | - | - | [34] | |
Intratumoral, stromal and total cells: CD3+, CD4+ and CD8+ * T cells, Tregs, B cells, NK cells, CD68+ and CD163+ macrophages | - | - | No | DFI/OS | UV | |||
Low stromal CD8+ T cells | - | 15.5 months | Yes | DFI/OS | UV | |||
High stromal CD8+ T cells | - | 31.0 months | ||||||
150 | Peritumoral inflammation distribution | Absent from focal | 5.3% | - | - | - | - | [109] |
Multifocal to diffuse | 94.7% | - | - | - | - | |||
Intratumoral inflammation distribution | Absent from focal | 28.7% | - | - | - | - | ||
Multifocal to diffuse | 71.3% | - | - | - | - | |||
Perilesional inflammation intensity | Discrete | 34.2% | - | - | - | - | ||
Moderate to marked | 65.8% | - | - | - | - | |||
Intratumoral inflammation intensity | Discrete | 58.2% | - | - | - | - | ||
Moderate to marked | 41.8% | - | - | - | - | |||
Tertiary lymphoid structures (present vs. absent) | 11.7% | - | - | - | - |
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Rodrigues-Jesus, J.; Canadas-Sousa, A.; Vilhena, H.; Dias-Pereira, P. Inside the Tumor: Decoding the Feline Mammary Tumor Microenvironment and Its Prognostic Value—A Review. Vet. Sci. 2025, 12, 959. https://doi.org/10.3390/vetsci12100959
Rodrigues-Jesus J, Canadas-Sousa A, Vilhena H, Dias-Pereira P. Inside the Tumor: Decoding the Feline Mammary Tumor Microenvironment and Its Prognostic Value—A Review. Veterinary Sciences. 2025; 12(10):959. https://doi.org/10.3390/vetsci12100959
Chicago/Turabian StyleRodrigues-Jesus, Joana, Ana Canadas-Sousa, Hugo Vilhena, and Patrícia Dias-Pereira. 2025. "Inside the Tumor: Decoding the Feline Mammary Tumor Microenvironment and Its Prognostic Value—A Review" Veterinary Sciences 12, no. 10: 959. https://doi.org/10.3390/vetsci12100959
APA StyleRodrigues-Jesus, J., Canadas-Sousa, A., Vilhena, H., & Dias-Pereira, P. (2025). Inside the Tumor: Decoding the Feline Mammary Tumor Microenvironment and Its Prognostic Value—A Review. Veterinary Sciences, 12(10), 959. https://doi.org/10.3390/vetsci12100959