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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

Infiltration of CD68+ tumor-associated macrophages (TAMs) according to breast cancer subtype.The levels of intratumoral (A), stromal (B), and total (C) TAMs are different according to breast cancer subtype. They are significantly lower in luminal A subtype than in luminal B, HER2+ and triple-negative subtypes. The box shows the first to third quartiles of TAMs infiltration levels, the horizontal line inside the box represents the median, the whiskers extend to minimum and maximum values within 1.5 times the interquartile range (IQR) from the first and third quartiles. Outliers are represented by small circles and, extreme values (more than 3 times IQR), by asterisks.
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pone.0125728.g002: Infiltration of CD68+ tumor-associated macrophages (TAMs) according to breast cancer subtype.The levels of intratumoral (A), stromal (B), and total (C) TAMs are different according to breast cancer subtype. They are significantly lower in luminal A subtype than in luminal B, HER2+ and triple-negative subtypes. The box shows the first to third quartiles of TAMs infiltration levels, the horizontal line inside the box represents the median, the whiskers extend to minimum and maximum values within 1.5 times the interquartile range (IQR) from the first and third quartiles. Outliers are represented by small circles and, extreme values (more than 3 times IQR), by asterisks.

Mentions: First, we measured the extent of intratumoral and stromal infiltration of TAMs in each tumor in the first set (Fig 1). TAM infiltration levels were variable. The median numbers of intratumoral and stromal TAMs per high-power field were 24.2 (interquartile range: 15.6 to 35.3) and 35.3 (interquartile range: 24.2 to 48.0), respectively. The levels of infiltration of intratumoral, stromal, and total TAMs were highly correlated (intratumoral vs. stromal TAM, r = 0.912, p<0.001; intratumoral vs. total TAM, r = 0.972, p<0.001; stromal vs. total TAM, r = 0.983, p<0.001). The relationships between levels of TAM infiltration (low vs. high) and various clinicopathologic features of the tumors are shown in Table 1. High levels of infiltration of intratumoral, stromal and total TAMs were associated with high histologic grade, pushing border, p53 overexpression, high Ki-67 proliferation index, ER negativity and PR negativity. HER2 status was also positively correlated with stromal and total TAMs, and with intratumoral TAMs (with marginal significance) (p = 0.030, p = 0.008, p = 0.062, respectively). The extent of infiltration of TAMs also differed by breast cancer subtype (p<0.001 in all compartments, Chi-square test and one-way ANOVA test), being significantly lower in luminal A subtype than in luminal B, HER2+ and triple-negative subtypes (intratumoral, p = 0.008, p = 0.006, p<0.001; stromal, p = 0.005, p<0.001, p<0.001; total, p = 0.005, p<0.001, p<0.001, respectively, Turkey post hoc test; Fig 2).


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)

Infiltration of CD68+ tumor-associated macrophages (TAMs) according to breast cancer subtype.The levels of intratumoral (A), stromal (B), and total (C) TAMs are different according to breast cancer subtype. They are significantly lower in luminal A subtype than in luminal B, HER2+ and triple-negative subtypes. The box shows the first to third quartiles of TAMs infiltration levels, the horizontal line inside the box represents the median, the whiskers extend to minimum and maximum values within 1.5 times the interquartile range (IQR) from the first and third quartiles. Outliers are represented by small circles and, extreme values (more than 3 times IQR), by asterisks.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0125728.g002: Infiltration of CD68+ tumor-associated macrophages (TAMs) according to breast cancer subtype.The levels of intratumoral (A), stromal (B), and total (C) TAMs are different according to breast cancer subtype. They are significantly lower in luminal A subtype than in luminal B, HER2+ and triple-negative subtypes. The box shows the first to third quartiles of TAMs infiltration levels, the horizontal line inside the box represents the median, the whiskers extend to minimum and maximum values within 1.5 times the interquartile range (IQR) from the first and third quartiles. Outliers are represented by small circles and, extreme values (more than 3 times IQR), by asterisks.
Mentions: First, we measured the extent of intratumoral and stromal infiltration of TAMs in each tumor in the first set (Fig 1). TAM infiltration levels were variable. The median numbers of intratumoral and stromal TAMs per high-power field were 24.2 (interquartile range: 15.6 to 35.3) and 35.3 (interquartile range: 24.2 to 48.0), respectively. The levels of infiltration of intratumoral, stromal, and total TAMs were highly correlated (intratumoral vs. stromal TAM, r = 0.912, p<0.001; intratumoral vs. total TAM, r = 0.972, p<0.001; stromal vs. total TAM, r = 0.983, p<0.001). The relationships between levels of TAM infiltration (low vs. high) and various clinicopathologic features of the tumors are shown in Table 1. High levels of infiltration of intratumoral, stromal and total TAMs were associated with high histologic grade, pushing border, p53 overexpression, high Ki-67 proliferation index, ER negativity and PR negativity. HER2 status was also positively correlated with stromal and total TAMs, and with intratumoral TAMs (with marginal significance) (p = 0.030, p = 0.008, p = 0.062, respectively). The extent of infiltration of TAMs also differed by breast cancer subtype (p<0.001 in all compartments, Chi-square test and one-way ANOVA test), being significantly lower in luminal A subtype than in luminal B, HER2+ and triple-negative subtypes (intratumoral, p = 0.008, p = 0.006, p<0.001; stromal, p = 0.005, p<0.001, p<0.001; total, p = 0.005, p<0.001, p<0.001, respectively, Turkey post hoc test; Fig 2).

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