Limits...
Prognostic value of tumor-associated macrophages according to histologic locations and hormone receptor status in breast cancer.

Gwak JM, Jang MH, Kim DI, Seo AN, Park SY - PLoS ONE (2015)

Bottom Line: Tumor-associated macrophages (TAMs) are involved in tumor progression by promoting epithelial-mesenchymal transition (EMT), tumor cell invasion, migration and angiogenesis.Finally, we analyzed the prognostic value of TAM levels according to hormone receptor status.Overall, a high level of infiltration of intratumoral TAMs was associated with poor disease-free survival, and was found to be an independent prognostic factor.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.

ABSTRACT
Tumor-associated macrophages (TAMs) are involved in tumor progression by promoting epithelial-mesenchymal transition (EMT), tumor cell invasion, migration and angiogenesis. However, in breast cancer, the clinical relevance of the TAM infiltration according to distinct histologic locations (intratumoral vs. stromal) and hormone receptor status is unclear. We investigated the significance of the levels of TAM infiltration in distinct histologic locations in invasive breast cancer. We also examined the relationship of the TAM levels with the clinicopathologic features of tumors, expression of EMT markers, and clinical outcomes. Finally, we analyzed the prognostic value of TAM levels according to hormone receptor status. High levels of infiltration of intratumoral, stromal and total TAMs were associated with high histologic grade, p53 overexpression, high Ki-67 proliferation index and negative hormone receptor status. Infiltration of TAMs was also correlated with overexpression of vimentin, smooth muscle actin and alteration of β-catenin. Overall, a high level of infiltration of intratumoral TAMs was associated with poor disease-free survival, and was found to be an independent prognostic factor. In subgroup analyses by hormone receptor status, a high level of infiltration of intratumoral TAM was an independent prognostic factor in the hormone receptor-positive subgroup, but not in the hormone-receptor negative subgroup. Our findings suggest that intratumoral TAMs play an important role in tumor progression in breast cancer, especially in the hormone receptor-positive group, and the level of TAM infiltration may be used as a prognostic factor and even a therapeutic target in breast cancer.

No MeSH data available.


Related in: MedlinePlus

Representative examples showing association of tumor-associated macrophage (TAM) infiltration with expression of epithelial-mesenchymal transition markers.(A) A case with high levels of TAM infiltration shows vimentin and smooth muscle actin (SMA) expression, and alteration of β-catenin. (B) On the contrary, another case with low levels of TAM infiltration does not show vimentin and SMA expression, but reveals intact membranous expression of β-catenin. Original magnification, x200.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4401667&req=5

pone.0125728.g003: Representative examples showing association of tumor-associated macrophage (TAM) infiltration with expression of epithelial-mesenchymal transition markers.(A) A case with high levels of TAM infiltration shows vimentin and smooth muscle actin (SMA) expression, and alteration of β-catenin. (B) On the contrary, another case with low levels of TAM infiltration does not show vimentin and SMA expression, but reveals intact membranous expression of β-catenin. Original magnification, x200.

Mentions: The extent of infiltration of TAMs in all histological locations was related to the expression of EMT markers, including vimentin, smooth muscle actin (SMA) and β-catenin (Table 2; Fig 3). In the hormone receptor-positive group, only β-catenin alteration was associated with high infiltration of total TAMs (p = 0.046) (S4 Table). In the hormone receptor-negative group, β-catenin alteration was also correlated with elevated infiltration of intratumoral and stromal TAMs (p = 0.021, p = 0.017, respectively) (S5 Table).


Prognostic value of tumor-associated macrophages according to histologic locations and hormone receptor status in breast cancer.

Gwak JM, Jang MH, Kim DI, Seo AN, Park SY - PLoS ONE (2015)

Representative examples showing association of tumor-associated macrophage (TAM) infiltration with expression of epithelial-mesenchymal transition markers.(A) A case with high levels of TAM infiltration shows vimentin and smooth muscle actin (SMA) expression, and alteration of β-catenin. (B) On the contrary, another case with low levels of TAM infiltration does not show vimentin and SMA expression, but reveals intact membranous expression of β-catenin. Original magnification, x200.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401667&req=5

pone.0125728.g003: Representative examples showing association of tumor-associated macrophage (TAM) infiltration with expression of epithelial-mesenchymal transition markers.(A) A case with high levels of TAM infiltration shows vimentin and smooth muscle actin (SMA) expression, and alteration of β-catenin. (B) On the contrary, another case with low levels of TAM infiltration does not show vimentin and SMA expression, but reveals intact membranous expression of β-catenin. Original magnification, x200.
Mentions: The extent of infiltration of TAMs in all histological locations was related to the expression of EMT markers, including vimentin, smooth muscle actin (SMA) and β-catenin (Table 2; Fig 3). In the hormone receptor-positive group, only β-catenin alteration was associated with high infiltration of total TAMs (p = 0.046) (S4 Table). In the hormone receptor-negative group, β-catenin alteration was also correlated with elevated infiltration of intratumoral and stromal TAMs (p = 0.021, p = 0.017, respectively) (S5 Table).

Bottom Line: Tumor-associated macrophages (TAMs) are involved in tumor progression by promoting epithelial-mesenchymal transition (EMT), tumor cell invasion, migration and angiogenesis.Finally, we analyzed the prognostic value of TAM levels according to hormone receptor status.Overall, a high level of infiltration of intratumoral TAMs was associated with poor disease-free survival, and was found to be an independent prognostic factor.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.

ABSTRACT
Tumor-associated macrophages (TAMs) are involved in tumor progression by promoting epithelial-mesenchymal transition (EMT), tumor cell invasion, migration and angiogenesis. However, in breast cancer, the clinical relevance of the TAM infiltration according to distinct histologic locations (intratumoral vs. stromal) and hormone receptor status is unclear. We investigated the significance of the levels of TAM infiltration in distinct histologic locations in invasive breast cancer. We also examined the relationship of the TAM levels with the clinicopathologic features of tumors, expression of EMT markers, and clinical outcomes. Finally, we analyzed the prognostic value of TAM levels according to hormone receptor status. High levels of infiltration of intratumoral, stromal and total TAMs were associated with high histologic grade, p53 overexpression, high Ki-67 proliferation index and negative hormone receptor status. Infiltration of TAMs was also correlated with overexpression of vimentin, smooth muscle actin and alteration of β-catenin. Overall, a high level of infiltration of intratumoral TAMs was associated with poor disease-free survival, and was found to be an independent prognostic factor. In subgroup analyses by hormone receptor status, a high level of infiltration of intratumoral TAM was an independent prognostic factor in the hormone receptor-positive subgroup, but not in the hormone-receptor negative subgroup. Our findings suggest that intratumoral TAMs play an important role in tumor progression in breast cancer, especially in the hormone receptor-positive group, and the level of TAM infiltration may be used as a prognostic factor and even a therapeutic target in breast cancer.

No MeSH data available.


Related in: MedlinePlus