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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

Disease-free survival according to the degree of tumor-associated macrophage (TAM) infiltration in each compartment.High levels of infiltration of intratumoral (A), but not stromal (B) and total (C) TAM, are associated with poor disease-free survival of the entire population of patients. However, in the hormone receptor (HR)-positive group, high levels of infiltration of intratumoral (D), stromal (E) and total (F) TAMs are each associated with decreased disease-free survival.
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pone.0125728.g004: Disease-free survival according to the degree of tumor-associated macrophage (TAM) infiltration in each compartment.High levels of infiltration of intratumoral (A), but not stromal (B) and total (C) TAM, are associated with poor disease-free survival of the entire population of patients. However, in the hormone receptor (HR)-positive group, high levels of infiltration of intratumoral (D), stromal (E) and total (F) TAMs are each associated with decreased disease-free survival.

Mentions: We also investigated the prognostic significance of TAM infiltration levels according to the different histologic locations and hormone receptor status in the first set. Most patients were treated by the standard practice guidelines and have been followed regularly after surgery. The median follow-up period was 7.7 years at the time of analysis (range, 0.1~10.6 years). There were 6 (2.2%) loco-regional recurrences and twenty-two (8.0%) distant metastases as first events. In the entire tumor sample, high infiltration levels of intratumoral TAMs were associated with decreased disease-free survival (p = 0.021; Fig 4A; Table 3). Elevated stromal and total TAM levels tended to be associated with poor disease-free survival (p = 0.084, p = 0.135, respectively; Fig 4B and 4C). In a multivariate analysis including T stage, N stage, lymphovascular invasion and intratumoral TAMs, high infiltration of intratumoral TAMs (hazard ratio, 2.810; 95% confidence interval, 1.064–7.416; p = 0.037) remained an independent prognostic indicator of poor disease-free survival.


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)

Disease-free survival according to the degree of tumor-associated macrophage (TAM) infiltration in each compartment.High levels of infiltration of intratumoral (A), but not stromal (B) and total (C) TAM, are associated with poor disease-free survival of the entire population of patients. However, in the hormone receptor (HR)-positive group, high levels of infiltration of intratumoral (D), stromal (E) and total (F) TAMs are each associated with decreased disease-free survival.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0125728.g004: Disease-free survival according to the degree of tumor-associated macrophage (TAM) infiltration in each compartment.High levels of infiltration of intratumoral (A), but not stromal (B) and total (C) TAM, are associated with poor disease-free survival of the entire population of patients. However, in the hormone receptor (HR)-positive group, high levels of infiltration of intratumoral (D), stromal (E) and total (F) TAMs are each associated with decreased disease-free survival.
Mentions: We also investigated the prognostic significance of TAM infiltration levels according to the different histologic locations and hormone receptor status in the first set. Most patients were treated by the standard practice guidelines and have been followed regularly after surgery. The median follow-up period was 7.7 years at the time of analysis (range, 0.1~10.6 years). There were 6 (2.2%) loco-regional recurrences and twenty-two (8.0%) distant metastases as first events. In the entire tumor sample, high infiltration levels of intratumoral TAMs were associated with decreased disease-free survival (p = 0.021; Fig 4A; Table 3). Elevated stromal and total TAM levels tended to be associated with poor disease-free survival (p = 0.084, p = 0.135, respectively; Fig 4B and 4C). In a multivariate analysis including T stage, N stage, lymphovascular invasion and intratumoral TAMs, high infiltration of intratumoral TAMs (hazard ratio, 2.810; 95% confidence interval, 1.064–7.416; p = 0.037) remained an independent prognostic indicator of poor disease-free survival.

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