The online version of this article (doi:10.1186/1757-2215-7-19) contains supplementary material, which is available to authorized users.
Meiying Zhang, Yifeng He contributed equally to this work.
The authors declare that they have no competing interests.
YFH, AMZ, and WD designed the study. MYZ performed the immunohistochemistry and immunofluorescence work. YFH and XJS independently reviewed the immunostained cancer tissue sections. WJW and QL performed the LCM and flow cytometry. YFH wrote the manuscript. All authors read and approved the final manuscript.
Tumor-associated macrophages (TAMs) are classified into two major phenotypes, M1 and M2. M1 TAMs suppress cancer progression, while M2 TAMs promote it. However, little is known regarding the role of TAMs in the development of ovarian cancer. Here, we investigated the relationship between TAM distribution patterns (density, microlocalization, and differentiation) and ovarian cancer histotypes, and we explored whether altered TAM distribution patterns influence long-term outcomes in ovarian cancer patients.
A total of 112 ovarian cancer patients were enrolled in this study, and the subjects were divided into two groups according to their survival (< 5 years vs. ≥ 5 years). Immunohistochemistry and immunofluorescence were used to determine the density, microlocalization, and differentiation status of TAMs in ovarian cancer tissues for each histotype. Kaplan-Meier survival and multivariate Cox regression analyses were used to evaluate the prognostic significance of TAM-related parameters in ovarian cancer.
TAMs most frequently infiltrated into the cancer tissue of the serous histotype, followed by mucinous, undifferentiated, endometrioid, and clear cell histotypes (p = 0.049). The islet/stroma ratio of total TAMs varied among the cancer histotypes, with mucinous and undifferentiated cancers displaying the lowest and highest ratios, respectively (p = 0.005). The intratumoral TAM density significantly increased with increasing cancer stage and grade (p = 0.023 and 0.006, respectively). However, the overall M1/M2 TAM ratio decreased as the cancer stage increased (p = 0.012). In addition, the intra-islet M1/M2 ratio inversely correlated with the residual site size (p = 0.004). Among the TAM-related parameters, only the increased overall and intra-islet M1/M2 TAM ratios displayed prognostic significance in both the Kaplan-Meier survival and multivariate Cox regression analyses; however, the values of these two parameters did not differ significantly among the cancer histotypes.
The patients with increased overall or intra-islet M1/M2 TAM ratios presented with an improved 5-year prognosis. Nevertheless, the TAM distribution patterns did not influence the overall outcomes of different ovarian cancer histotypes.
Additional file 1: Tables S1-S14: Describe the multivariate Cox regression analytic results for the following TAM-related parameters (for the overall M1/M2 TAM ratio, see Table 4): total TAM density (Table S1); intra-islet TAM density (Table S2); intra-stromal TAM density (Table S3); overall M1 TAM density (Table S4); intra-islet M1 TAM density (Table S5); intra-stromal M1 TAM density (Table S6); overall M2 TAM density (Table S7); intra-islet M2 TAM density (Table S8); intra-stromal M2 TAM density (Table S9); islet/stroma ratio of total TAMs (Table S10); islet/stroma ratio of M1 TAMs (Table S11); islet/stroma ratio of M2 TAMs (Table S12); intra-islet M1/M2 TAM ratio (Table S13); and intra-stromal M1/M2 TAM ratio (Table S14). (PDF 805 KB)
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- A high M1/M2 ratio of tumor-associated macrophages is associated with extended survival in ovarian cancer patients
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