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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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Kaplan Meier analysis of BT3.2 in high-grade serous EOC.Kaplan-Meier curves of overall survival (A) and disease-free survival (B) in 194 and 171 patients, respectively. Significance (p) is indicated by log rank.
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pone-0038541-g002: Kaplan Meier analysis of BT3.2 in high-grade serous EOC.Kaplan-Meier curves of overall survival (A) and disease-free survival (B) in 194 and 171 patients, respectively. Significance (p) is indicated by log rank.

Mentions: Kaplan-Meier curves showed that there was a strong association between high expression of BT3.2 protein and increased overall patient survival (p = 0.014; log rank = 6.03) (Figure 2A). Mean survival interval was 85 months for patients with higher level of BT3.2 compared with 59 months for patients with low level of BT3.2. Similarly, patients with higher expression of BT3.2 had a mean progression interval of 86 months compared to 55 months for patients with low expression of BT3.2 (p = 0.002, log rank = 9.65) (Figure 2B).


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)

Kaplan Meier analysis of BT3.2 in high-grade serous EOC.Kaplan-Meier curves of overall survival (A) and disease-free survival (B) in 194 and 171 patients, respectively. Significance (p) is indicated by log rank.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369854&req=5

pone-0038541-g002: Kaplan Meier analysis of BT3.2 in high-grade serous EOC.Kaplan-Meier curves of overall survival (A) and disease-free survival (B) in 194 and 171 patients, respectively. Significance (p) is indicated by log rank.
Mentions: Kaplan-Meier curves showed that there was a strong association between high expression of BT3.2 protein and increased overall patient survival (p = 0.014; log rank = 6.03) (Figure 2A). Mean survival interval was 85 months for patients with higher level of BT3.2 compared with 59 months for patients with low level of BT3.2. Similarly, patients with higher expression of BT3.2 had a mean progression interval of 86 months compared to 55 months for patients with low expression of BT3.2 (p = 0.002, log rank = 9.65) (Figure 2B).

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