title: A high M1/M2 ratio of tumor-associated macrophages is associated with extended survival in ovarian cancer patients.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Meiying
authors: M
authors: Zhang
authors: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China. he_yifeng@hotmail.com.
authors: Yifeng
authors: Y
authors: He
authors: Xiangjun
authors: X
authors: Sun
authors: Qing
authors: Q
authors: Li
authors: Wenjing
authors: W
authors: Wang
authors: Aimin
authors: A
authors: Zhao
authors: Wen
authors: W
authors: Di
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002454:Cell Differentiation; D016009:Chi-Square Distribution; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000737:chemistry / Q000276:immunology*; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D010641:Phenotype; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor