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Mixed-polarization phenotype of ascites-associated macrophages in human ovarian carcinoma: correlation of CD163 expression, cytokine levels and early relapse.

Reinartz S, Schumann T, Finkernagel F, Wortmann A, Jansen JM, Meissner W, Krause M, Schwörer AM, Wagner U, Müller-Brüsselbach S, Müller R - Int. J. Cancer (2013)

Bottom Line: However, global gene expression profiles determined for 17 of these patients revealed a mixed-polarization phenotype unrelated to the M1/M2 classification.CD163 surface expression also correlated with the ascites levels of IL-6 and IL-10 (p < 0.05), both cytokines induced CD163 expression, and their ascites levels showed a clear inverse association with RFS (p < 0.01).These findings define a subgroup of patients with high CD163 expression, high IL-6 and/or IL-10 levels and poor clinical outcome.

View Article: PubMed Central - PubMed

Affiliation: Clinic for Gynecology, Gynecological Oncology and Gynecological Endocrinology, Philipps University, Marburg, Germany.

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Association of RFS with CD163 surface expression on ovarian carcinoma TAMs. Kaplan–Meier plots showing the RFS of patients with high or low levels (median centered) of CD14 (% of leukocytes; panel a), CD163 (% of CD14+; panel b), CD206 (% of CD14+; panel c), CD32 (MFI; panel d), CD68 (% of CD14+; panel e) and CCR7 (% of CD14+; panel f) expression on their TAMs. p-Values were determined by Mantel–Cox log-rank test.
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fig02: Association of RFS with CD163 surface expression on ovarian carcinoma TAMs. Kaplan–Meier plots showing the RFS of patients with high or low levels (median centered) of CD14 (% of leukocytes; panel a), CD163 (% of CD14+; panel b), CD206 (% of CD14+; panel c), CD32 (MFI; panel d), CD68 (% of CD14+; panel e) and CCR7 (% of CD14+; panel f) expression on their TAMs. p-Values were determined by Mantel–Cox log-rank test.

Mentions: We first analyzed potential correlations between the expression of macrophage polarization surface markers and clinical progression. All patients with a postsurgery period of at least 6 months (range 6–24 months) were included in our study (n = 20). For each marker, patients were grouped as “high” or “low” using the respective median as a cutoff point, as shown in Figures 1a–1f. These datasets were analyzed for association with relapse-free survival (RFS). Although macrophage density (% CD14+ cells of total leukocytes) was not associated with RFS (log-rank test, p = 0.7241; Fig. 2a), we found an inverse association between RFS and expression of the M2 marker CD163 (hemoglobin/haptoglobin scavenger receptor; p = 0.0496; Fig. 2b). In contrast, no association was observed for another M2 marker, the mannose receptor CD206 (p > 0.7; Figs. 1d and 2c). Similarly, other markers connected to macrophage polarization did not show any association with clinical progression (CD32, CD68 and CCR7 in Figs. 2d and 2e; all p-values > 0.8). A similar negative result was obtained with CD16, CD64, HLA-DR and intracellular IL-10/IL-12 ratio (all p-values > 0.6). Furthermore, no correlation was seen between histological grading and RFS (p > 0.1).


Mixed-polarization phenotype of ascites-associated macrophages in human ovarian carcinoma: correlation of CD163 expression, cytokine levels and early relapse.

Reinartz S, Schumann T, Finkernagel F, Wortmann A, Jansen JM, Meissner W, Krause M, Schwörer AM, Wagner U, Müller-Brüsselbach S, Müller R - Int. J. Cancer (2013)

Association of RFS with CD163 surface expression on ovarian carcinoma TAMs. Kaplan–Meier plots showing the RFS of patients with high or low levels (median centered) of CD14 (% of leukocytes; panel a), CD163 (% of CD14+; panel b), CD206 (% of CD14+; panel c), CD32 (MFI; panel d), CD68 (% of CD14+; panel e) and CCR7 (% of CD14+; panel f) expression on their TAMs. p-Values were determined by Mantel–Cox log-rank test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232932&req=5

fig02: Association of RFS with CD163 surface expression on ovarian carcinoma TAMs. Kaplan–Meier plots showing the RFS of patients with high or low levels (median centered) of CD14 (% of leukocytes; panel a), CD163 (% of CD14+; panel b), CD206 (% of CD14+; panel c), CD32 (MFI; panel d), CD68 (% of CD14+; panel e) and CCR7 (% of CD14+; panel f) expression on their TAMs. p-Values were determined by Mantel–Cox log-rank test.
Mentions: We first analyzed potential correlations between the expression of macrophage polarization surface markers and clinical progression. All patients with a postsurgery period of at least 6 months (range 6–24 months) were included in our study (n = 20). For each marker, patients were grouped as “high” or “low” using the respective median as a cutoff point, as shown in Figures 1a–1f. These datasets were analyzed for association with relapse-free survival (RFS). Although macrophage density (% CD14+ cells of total leukocytes) was not associated with RFS (log-rank test, p = 0.7241; Fig. 2a), we found an inverse association between RFS and expression of the M2 marker CD163 (hemoglobin/haptoglobin scavenger receptor; p = 0.0496; Fig. 2b). In contrast, no association was observed for another M2 marker, the mannose receptor CD206 (p > 0.7; Figs. 1d and 2c). Similarly, other markers connected to macrophage polarization did not show any association with clinical progression (CD32, CD68 and CCR7 in Figs. 2d and 2e; all p-values > 0.8). A similar negative result was obtained with CD16, CD64, HLA-DR and intracellular IL-10/IL-12 ratio (all p-values > 0.6). Furthermore, no correlation was seen between histological grading and RFS (p > 0.1).

Bottom Line: However, global gene expression profiles determined for 17 of these patients revealed a mixed-polarization phenotype unrelated to the M1/M2 classification.CD163 surface expression also correlated with the ascites levels of IL-6 and IL-10 (p < 0.05), both cytokines induced CD163 expression, and their ascites levels showed a clear inverse association with RFS (p < 0.01).These findings define a subgroup of patients with high CD163 expression, high IL-6 and/or IL-10 levels and poor clinical outcome.

View Article: PubMed Central - PubMed

Affiliation: Clinic for Gynecology, Gynecological Oncology and Gynecological Endocrinology, Philipps University, Marburg, Germany.

Show MeSH
Related in: MedlinePlus