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BTN3A2 expression in epithelial ovarian cancer is associated with higher tumor infiltrating T cells and a better prognosis.

Le Page C, Marineau A, Bonza PK, Rahimi K, Cyr L, Labouba I, Madore J, Delvoye N, Mes-Masson AM, Provencher DM, Cailhier JF - PLoS ONE (2012)

Bottom Line: BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC).In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome.While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells.

View Article: PubMed Central - PubMed

Affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.

ABSTRACT
BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the only known role of butyrophilin proteins is in immune regulation, we evaluated the association between BT3.2 expression and intratumoral infiltration of immune cells by immunohistochemistry with specific antibodies against BT3.2, CD3, CD4, CD8, CD20, CD68 and CD206. Epithelial BT3.2 expression was significantly associated with longer overall survival and lower risk of disease progression (HR=0.651, p=0.006 and HR=0.642, p=0.002, respectively) and significantly associated with a higher density of infiltrating T cells, particularly CD4+ cells (0.272, p<0.001). We also observed a strong association between the relative density of CD206+ cells, as evaluated by the ratio of intratumoral CD206+/CD68+ expression, and risk of disease progression (HR=1.355 p=0.044, respectively). In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome. In contrast, high CD206+/CD68+ expression is associated with high risk of disease progression. While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells.

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Related in: MedlinePlus

Representative staining for immunohistochemistry of infiltrating macrophages.High and low density of CD68+ (tumor-associated macrophages, TAM) (A) and CD206+ (M2 subtype of TAM) cells (B). Magnification in the high infiltration area is shown on the right panel for each staining (top). C and D. Kaplan-Meier analysis of the ratio of infiltrating intraepithelial CD206+/CD68+ cells representing the relative density of CD206+ M2 TAM over the total density of CD68+ intraepithelial infiltrating macrophages. Kaplan-Meier curves of overall survival (C) and disease-free survival (D) in 180 and 174 patients, respectively. Significance (p) is indicated by log rank.
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pone-0038541-g004: Representative staining for immunohistochemistry of infiltrating macrophages.High and low density of CD68+ (tumor-associated macrophages, TAM) (A) and CD206+ (M2 subtype of TAM) cells (B). Magnification in the high infiltration area is shown on the right panel for each staining (top). C and D. Kaplan-Meier analysis of the ratio of infiltrating intraepithelial CD206+/CD68+ cells representing the relative density of CD206+ M2 TAM over the total density of CD68+ intraepithelial infiltrating macrophages. Kaplan-Meier curves of overall survival (C) and disease-free survival (D) in 180 and 174 patients, respectively. Significance (p) is indicated by log rank.

Mentions: As seen in Figure 3 and Figure 4A-B, immune infiltration of T cells, B cells and TAM was observed in EOC tissues at various densities in the intraepithelial areas. The intraepithelial infiltration of T cells, CD3+, CD4+ or CD8+, was highly correlated with the presence of CD20+ B cells (p<0.001) and CD68+ macrophages (P<0.001), including the CD206+ cells (Table 4). The intraepithelial infiltration of B cells was also associated with the presence of CD68+ and CD206+ cells (r = 0.364 and r = 0.171, p<0.001 and p = 0.022, respectively). Interestingly, the proportion of CD206+ cells relative to the total density of CD68+ macrophages, the ratio CD206+/CD68+ expression, was inversely correlated to the presence of CD3+T cells and tended to correlate with the presence of B cells (r = -0.216, p = 0.005 and r = -0.141, p = 0.063, respectively) (Table 4).


BTN3A2 expression in epithelial ovarian cancer is associated with higher tumor infiltrating T cells and a better prognosis.

Le Page C, Marineau A, Bonza PK, Rahimi K, Cyr L, Labouba I, Madore J, Delvoye N, Mes-Masson AM, Provencher DM, Cailhier JF - PLoS ONE (2012)

Representative staining for immunohistochemistry of infiltrating macrophages.High and low density of CD68+ (tumor-associated macrophages, TAM) (A) and CD206+ (M2 subtype of TAM) cells (B). Magnification in the high infiltration area is shown on the right panel for each staining (top). C and D. Kaplan-Meier analysis of the ratio of infiltrating intraepithelial CD206+/CD68+ cells representing the relative density of CD206+ M2 TAM over the total density of CD68+ intraepithelial infiltrating macrophages. Kaplan-Meier curves of overall survival (C) and disease-free survival (D) in 180 and 174 patients, respectively. Significance (p) is indicated by log rank.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3369854&req=5

pone-0038541-g004: Representative staining for immunohistochemistry of infiltrating macrophages.High and low density of CD68+ (tumor-associated macrophages, TAM) (A) and CD206+ (M2 subtype of TAM) cells (B). Magnification in the high infiltration area is shown on the right panel for each staining (top). C and D. Kaplan-Meier analysis of the ratio of infiltrating intraepithelial CD206+/CD68+ cells representing the relative density of CD206+ M2 TAM over the total density of CD68+ intraepithelial infiltrating macrophages. Kaplan-Meier curves of overall survival (C) and disease-free survival (D) in 180 and 174 patients, respectively. Significance (p) is indicated by log rank.
Mentions: As seen in Figure 3 and Figure 4A-B, immune infiltration of T cells, B cells and TAM was observed in EOC tissues at various densities in the intraepithelial areas. The intraepithelial infiltration of T cells, CD3+, CD4+ or CD8+, was highly correlated with the presence of CD20+ B cells (p<0.001) and CD68+ macrophages (P<0.001), including the CD206+ cells (Table 4). The intraepithelial infiltration of B cells was also associated with the presence of CD68+ and CD206+ cells (r = 0.364 and r = 0.171, p<0.001 and p = 0.022, respectively). Interestingly, the proportion of CD206+ cells relative to the total density of CD68+ macrophages, the ratio CD206+/CD68+ expression, was inversely correlated to the presence of CD3+T cells and tended to correlate with the presence of B cells (r = -0.216, p = 0.005 and r = -0.141, p = 0.063, respectively) (Table 4).

Bottom Line: BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC).In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome.While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells.

View Article: PubMed Central - PubMed

Affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.

ABSTRACT
BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the only known role of butyrophilin proteins is in immune regulation, we evaluated the association between BT3.2 expression and intratumoral infiltration of immune cells by immunohistochemistry with specific antibodies against BT3.2, CD3, CD4, CD8, CD20, CD68 and CD206. Epithelial BT3.2 expression was significantly associated with longer overall survival and lower risk of disease progression (HR=0.651, p=0.006 and HR=0.642, p=0.002, respectively) and significantly associated with a higher density of infiltrating T cells, particularly CD4+ cells (0.272, p<0.001). We also observed a strong association between the relative density of CD206+ cells, as evaluated by the ratio of intratumoral CD206+/CD68+ expression, and risk of disease progression (HR=1.355 p=0.044, respectively). In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome. In contrast, high CD206+/CD68+ expression is associated with high risk of disease progression. While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells.

Show MeSH
Related in: MedlinePlus