Macrophage infiltration and its prognostic implications in breast cancer: The relationship with VEGF expression and microvessel density

Tsutsui, Shinichi; Yasuda, Kazuhiro; Suzuki, Kosuke; Tahara, Kenji; Higashi, Hidefumi; Era, Shoichi

doi:10.3892/or.14.2.425

Cited by 233 publications

(268 citation statements)

References 0 publications

Supporting

Mentioning

247

Contrasting

Unclassified

Order By: Relevance

“…HR associated with Ki-67 positivity in this case) from studies with inherent dissimilarities. The observed disparity among the conclusions of different studies, responsible for the observed heterogeneity, can be quantified by applying Bukholm et al (2003) 147 No Ceccarelli et al (2000) 217 Yes Galiegue et al (2004) 117 No Gasparini et al (1992) 164 Yes Haerslev et al (1996) 487 Yes Jalava et al (2000) 414 No Kroger et al (2006) 157 No Kronblad et al (2006) 377 Yes Lampe et al (1998) 142 Yes Liu et al (2000) 225 Yes Michels et al (2003) 104 No Molino et al (1997) 322 Yes Rudas et al (1994) 184 No Tsutsui et al (2005) 249 Yes Yang et al (2003) 147 No…”

Section: Discussionmentioning

confidence: 99%

Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients

et al. 2007

View full text Add to dashboard Cite

The Ki-67 antigen is used to evaluate the proliferative activity of breast cancer (BC); however, Ki-67's role as a prognostic marker in BC is still undefined. In order to better define the prognostic value of Ki-67/MIB-1, we performed a meta-analysis of studies that evaluated the impact of Ki-67/MIB-1 on disease-free survival (DFS) and/or on overall survival (OS) in early BC. Sixty-eight studies were identified and 46 studies including 12 155 patients were evaluable for our meta-analysis; 38 studies were evaluable for the aggregation of results for DFS, and 35 studies for OS. Patients were considered to present positive tumours for the expression of Ki-67/MIB-1 according to the cut-off points defined by the authors. Ki-67/MIB-1 positivity is associated with higher probability of relapse in all patients (HR ¼ 1.93 (95% confidence interval (CI): 1.74 -2.14); Po0.001), in node-negative patients (HR ¼ 2.31 (95% CI: 1.83 -2.92); Po0.001) and in node-positive patients (HR ¼ 1.59 (95% CI: 1.35 -1.87); Po0.001). Furthermore, Ki-67/MIB-1 positivity is associated with worse survival in all patients (HR ¼ 1.95 (95% CI: 1.70 -2.24; Po0.001)), node-negative patients (HR ¼ 2.54 (95% CI: 1.65 -3.91); Po0.001) and node-positive patients (HR ¼ 2.33 (95% CI: 1.83 -2.95); Po0.001). Our meta-analysis suggests that Ki-67/ MIB-1 positivity confers a higher risk of relapse and a worse survival in patients with early BC.

show abstract

Section: Discussionmentioning

confidence: 99%

Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients

et al. 2007

View full text Add to dashboard Cite

show abstract

“…In addition, the density of tumor-associated macrophages (TAMs) in many tumors correlates with increased angiogenesis, tumor invasion and poor prognosis. [29][30][31] TAMs derive from circulating monocytes, which are selectively recruited to the tumor microenvironment by locally produced chemotactic factors. 32,33 metastasis.…”

Section: Tumor Immunologymentioning

confidence: 99%

The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas

et al. 2014

View full text Add to dashboard Cite

Increasing evidence indicates the involvement of inflammation and coagulation in cancer progression and metastases. Inflammatory biomarkers hold great promise for improving the predictive ability of existing prognostic tools in cancer patients. In the present study, we investigated several inflammatory indices with regard to their prognostic relevance for predicting clinical outcome in soft tissue sarcoma (STS) patients. Three hundred and forty STS patients were divided into a training set (n 5 170) and a validation set (n 5 170). Besides well-established clinico-pathological prognostic factors, we evaluated the prognostic value of the neutrophil/lymphocyte (N/L) ratio, the lymphocyte/monocyte (L/M) ratio and the platelet/lymphocyte (P/L) ratio using Kaplan-Meier curves and univariate as well as multivariate Cox regression models. Additionally, we developed a nomogram by supplementing the L/M ratio to the well-established Kattan nomogram and evaluated the predictive accuracy of this novel nomogram by applying calibration and Harrell's concordance index (c-index). In multivariate analysis, a low L/M ratio was significantly associated with decreased CSS and DFS (HR 5 0.41, 95% CI 5 0.18-0.97, p 5 0.043; HR 5 0.39, 95% CI 5 0.16-0.91, p 5 0.031, respectively) in the training set. Using the validation set for confirmation, we found also in multivariate analysis an independent value for CSS (HR 5 0.33, 95% CI 5 0.12-0.90, p 5 0.03) and for DFS (HR 5 0.36, 95% CI 5 0.16-0.79, p 5 0.01). The estimated c-index was 0.74 using the original Kattan nomogram and 0.78 when the L/M ratio was added. Our study reports for the first time that the pre-operative L/M ratio represents a novel independent prognostic factor for prediction the clinical outcome in STS patients. This easily determinable biomarker might be helpful in improved individual risk assessment.Soft tissue sarcomas (STS) account for nearly 11,280 cases per year and are responsible for about 3,900 deaths in the United States annually, mainly due to local recurrence or metastatic disease. 1 Therefore, it is crucial to understand the biological mechanisms that contribute to tumor progression and to identify novel prognostic markers to generate individualized treatment and follow-up schedules. In a large retrospective study of 2,136 STS patients, Kattan et al. developed a postoperative prognostic model that predicts sarcomaspecific death, based on traditional prognostic factors such as age at diagnosis, tumor size, histologic grade, histologic subtype, tumor depth and site. 2 This nomogram is useful for general risk assessment and has potential value in determining surgical strategy and adjuvant management. Nevertheless, novel prognostic factors might be helpful in improving its predictive ability. Current approaches in cancer research have focused on the characterization of novel biomarkers, which ideally should be easily accessible, highly reproducible, cheap and most importantly, identify patients at high risk for disease-recurrence and death. Increasing evidence su...

show abstract

“…In comparison with conventional macrophages, tumor-associated macrophage (TAM) cells exhibit poor antigen-presenting capability, produce factors that suppress T-cell proliferation and activity, and are generally better adapted to scavenging debris, promoting angiogenesis, repairing and remodeling wounded/damaged tissues [3]. Recent studies show that TAM cells also play an essential role in inducing invasion and metastasis of breast tumors [4,5]. TAM cells secrets EGF to induce the proliferation and invasion of surrounding tissues by tumor cells [6].…”

Section: Introductionmentioning

confidence: 99%

Akt2 is required for macrophage chemotaxis

Zhang

Guo

et al. 2009

Eur J Immunol

View full text Add to dashboard Cite

Tumor-associated macrophages play an important role in tumorigenesis and metastasis. Trafficking of macrophages to the proximity of tumors is mediated by CSF-1, a growth factor. In this study, we investigated the role of PKB/Akt in CSF-1-induced macrophage migration. Disruption of Akt2 expression by small interference RNA impaired chemotaxis of both THP-1 cells and mouse peritoneal macrophages. Phosphorylation of PKCf, an essential component in chemotaxis signaling pathway, was reduced. LIMK/Cofilin, downstream of PKCf, regulated cytoskeleton rearrangement during cell migration. Disruption of Akt2 expression inhibited CSF-1-induced LIMK/Cofilin phosphorylation, which contributed to defects in actin polymerization and chemotaxis. Furthermore, MCP-1, a chemokine, -induced macrophage chemotaxis was also impaired. Taken together, our results demonstrated that Akt2 plays an essential role in both CSF-1-and chemokine-induced chemotaxis of macrophages.Key words: Chemokine . CSF-1 . Metastasis . Tumor-associated macrophages IntroductionChronicle inflammation promotes, sometimes even induces, tumorigenesis [1,2]. Tumor attracts macrophages and induces their differentiation by secreting . In comparison with conventional macrophages, tumor-associated macrophage (TAM) cells exhibit poor antigen-presenting capability, produce factors that suppress T-cell proliferation and activity, and are generally better adapted to scavenging debris, promoting angiogenesis, repairing and remodeling wounded/damaged tissues [3]. Recent studies show that TAM cells also play an essential role in inducing invasion and metastasis of breast tumors [4,5]. TAM cells secrets EGF to induce the proliferation and invasion of surrounding tissues by tumor cells [6]. Eventually, migratory cancer cells follow EGF gradient, enter the circulation, and spread throughout the body. Depletion of macrophages effectively blocked metastasis in a mouse model [7]. Thus, disrupt of TAM function will provide a novel approach to develop anti-cancer therapies.Recruitment of macrophages to the proximity of tumors was mediated by CSF-1, a growth factor, secreted by tumor cells [6]. CSF-1 also stimulates the proliferation, differentiation, and survival of macrophages [8]. Macrophages stimulated with CSF-1 show immediate cell polarization, actin reorganization, and migration to the CSF-1 secreting tumor cells [9]. Extensive studies have revealed the molecular mechanism of chemokine receptor, a subfamily of G-protein-coupled receptors, -mediated leukocyte trafficking during inflammation [10,11]. However, the signal transduction pathway that regulates CSF-1-induced macrophage migration is still largely unknown. Investigating molecular mechanism of CSF-1-mediated macrophage chemotaxis will provide new insights to block the formation and accumulation of TAM cells.The Akt/PKB family, Akt1, 2, and 3, plays a critical role in regulating cell growth, proliferation, survival, and metabolism [12,13]. Akt1 and 2 are expressed in most cell types and tissues 894while Akt3 shows a more r...

show abstract

Macrophage infiltration and its prognostic implications in breast cancer: The relationship with VEGF expression and microvessel density

Cited by 233 publications

References 0 publications

Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients

Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients

The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas

Akt2 is required for macrophage chemotaxis

Contact Info

Product

Resources

About