Table 2.
Representative studies demonstrating the association of TAMs with tumor progression parameters in breast cancer.
| Cohort of patients | Method of detection | TAM correlation with tumor growth and stage | TAM correlation with lymphatic and hematogenous metastasis | TAM correlation with survival | Reference |
|---|---|---|---|---|---|
| 101 patients with invasive breast carcinoma (UK) | IHC (Chalkley point array) | Not studied | Not studied | Increase of CD68+ TAM amount above the median (12 per HPF ×250) correlates with relapse up to 3 times and with reduced OS rate by 25% | (61) |
| 60 primary BC (Egypt) | IHC (manually) | Increased stromal CD68+ TAM amount above the median (35.3 per hot spot ×400) is indicative for larger tumor size (>5 cm) | Increased stromal CD68+ TAM amount above the median (35.3 per hot spot ×400) correlates with LN metastasis and vascular invasion | Not studied | (62) |
| 371 patients with invasive BC (USA) | Multiplex-IF in TMA (digital imaging scanning) | Presence of CD68+ TAMs positively is associated with tumor size, tumor grade and stage | Not studied | High amount of CD68+ (defined as score 3) and CD163+ (score 3 and 4) TAMs in tumor stroma correlates with reduced OS rate by 20% | (63) |
| 278 BC patients (Finland) | IHC (manually) | Increase of CD68+ TAM amount above the median (34 cells per hot spot ×400) is indicative for histological grade 3. Increase of CD163+ TAM amount above the median (26 cells per hot spot ×400) is indicative for large tumor size and grade 3 |
High amount of CD163+ TAMs (>26 per hot spot ×400) correlates with LN positivity | High amount of TAMs (CD68+ >34 and CD163+ >26 cells per hot spot ×400) correlates with reduced OS rate by 25% | (64) |
| 1,579 non-metastatic BC (China) | IHC (manually) | Increase of CD68+ and CD163+ TAM amount above the medians (33 and 21 cells, respectively, per HPF ×400) is indicative for histological grade 3 | High amount of CD68+CD163+ TAMs (>21 per hot spot ×400) correlates with positive LN status | High amount of CD163+ TAMs (>21 cells per HPF ×400) correlates with reduced OS rate by 10% | (65) |
| 367 non-metastatic primary invasive BC (South Korea) | IHC in TMA (manually) | 1.5-fold increased amount of CD68+ and twofold increased amount of CD163+ TAMs are indicative for tumors of grade 3 vs. grades 1–2 | Not significant | High amount of CD68+ TAMs (>33 cells per HPF ×400) in tumor nest correlates with reduced OS and DFS rates by 20% | (66) |
| 149 patients with invasive ductal carcinoma (Japan) | IHC (not specified) | High TAM density (>190 CD68+ cells/mm2, >145 CD163+ cells/mm2 and >200 CD204+ cells/mm2 per HPF ×200) is indicative for histological grades 2 and 3 | Not significant | Increase of CD204+ TAM density over 200 cells/mm2 correlates with reduced RFS, distant RFS and DSS rates by 25, 40 and 20%, respectively | (67) |
BC, breast cancer; DFS, disease-free survival; DSS, disease-specific survival; HPF, high-power field; IF, immunofluorescence; IHC, immunohistochemistry; LN, lymph node; TAM, tumor-associated macrophages; OS, overall survival; RFS, recurrence-free survival; TMA, tissue microarray.