Limits...
Cytotoxic T lymphocyte antigen 4 expression in human breast cancer: implications for prognosis.

Yu H, Yang J, Jiao S, Li Y, Zhang W, Wang J - Cancer Immunol. Immunother. (2015)

Bottom Line: Univariate analysis (log-rank) associated higher density of interstitial CTLA-4(+) lymphocytes with longer DFS and OS, but higher tumor CTLA-4 expression with shorter OS.These results indicated that CTLA-4 expression in lymphocytes was associated with better prognosis, but that in tumor cells was associated with worse prognosis.Patients' CTLA-4 profiles might thus be used to predict the benefits and toxicity of CTLA-4 blockade.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, General Hospital of Chinese People's Liberation Army, No. 28, Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China.

ABSTRACT
To examine the relationship between cytotoxic T lymphocyte antigen 4 (CTLA-4) expression and breast cancer prognosis, CTLA-4 expression was immunohistochemically detected in paraffin-embedded specimens of primary tumors from 130 patients with breast cancer who had a mean follow-up period of 112 months. CTLA-4 expressed in cytoplasm of breast cancer cells and in cytoplasm and cell membranes of interstitial lymphocytes. Univariate analysis (log-rank) associated higher density of interstitial CTLA-4(+) lymphocytes with longer DFS and OS, but higher tumor CTLA-4 expression with shorter OS. After controlling for age, clinical stage, Scarff-Bloom-Richardson grade, tumor thrombus, ER, PR, HER2 and Ki-67, multivariate analysis (Cox) showed that density of interstitial CTLA-4(+) lymphocytes independently predicted longer DFS (HR 0.315, P = 0.002) and OS (HR 0.313, P = 0.005), whereas tumor CTLA-4 expression independently predicted shorter DFS (HR 2.176, P = 0.029) and OS (HR 2.820, P = 0.007), i.e., patients with high CTLA-4(+) lymphocyte density and CTLA-4(low) tumor cells had the best prognoses. These results indicated that CTLA-4 expression in lymphocytes was associated with better prognosis, but that in tumor cells was associated with worse prognosis. Patients' CTLA-4 profiles might thus be used to predict the benefits and toxicity of CTLA-4 blockade.

Show MeSH

Related in: MedlinePlus

Kaplan–Meier survival curves on the correlation between favorable CTLA-4 expression profile and prognosis. Patients with high density CTLA-4+ interstitial lymphocytes (>33.44/mm2) and low CTLA-4 expression intensity in tumor cells (≤1.525) were characterized as the favorable CTLA-4 expression profile (FCEP) Group; the other patients were the Other Patients Group. Univariate analysis (log-rank) indicated that, the patients in FCEP group had longer DFS (a) and OS (b) than those of the Other Patients Group
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4481300&req=5

Fig2: Kaplan–Meier survival curves on the correlation between favorable CTLA-4 expression profile and prognosis. Patients with high density CTLA-4+ interstitial lymphocytes (>33.44/mm2) and low CTLA-4 expression intensity in tumor cells (≤1.525) were characterized as the favorable CTLA-4 expression profile (FCEP) Group; the other patients were the Other Patients Group. Univariate analysis (log-rank) indicated that, the patients in FCEP group had longer DFS (a) and OS (b) than those of the Other Patients Group

Mentions: Based on the aforementioned analysis, we renamed Group 1 as the “favorable CTLA-4 expression profile” (FCEP) Group, and patients in Groups 2, 3 and 4 collectively as the “Other Patients” Group. The HER-2+ rate was significantly lower in the FCEP Group than in Other Patients Group (12.50 vs. 34.92 %, P = 0.048, Pearson Chi-square test). But the two groups did not significantly differ in other clinical features. Univariate analysis (log-rank) showed the DFS of FCEP Group (N = 43, events = 3, mean DFS = 133.332 months) was longer than DFS of Other Patients Group(N = 85, events = 30, mean DFS = 108.384 months; P < 0.001), and OS of FCEP Group (N = 43, events = 2, mean OS = 134.782 months) was longer than OS of Other Patients Group(N = 85, events = 27, mean OS = 111.471 months; P = 0.001) (Fig. 2). Multivariate analysis showed that (after controlling for age, clinical stage, SBR grade, tumor thrombus, ER, PR, HER2 and Ki-67) FCEP status independently predicted longer DFS (HR 0.148, 95 % CL 0.045–0.489, P = 0.002) and OS (HR 0.116, 95 % CL 0.027–0.495, P = 0.004). Clinical stage, SBR grade and HER-2 were also independent predictors of DFS and OS.Fig. 2


Cytotoxic T lymphocyte antigen 4 expression in human breast cancer: implications for prognosis.

Yu H, Yang J, Jiao S, Li Y, Zhang W, Wang J - Cancer Immunol. Immunother. (2015)

Kaplan–Meier survival curves on the correlation between favorable CTLA-4 expression profile and prognosis. Patients with high density CTLA-4+ interstitial lymphocytes (>33.44/mm2) and low CTLA-4 expression intensity in tumor cells (≤1.525) were characterized as the favorable CTLA-4 expression profile (FCEP) Group; the other patients were the Other Patients Group. Univariate analysis (log-rank) indicated that, the patients in FCEP group had longer DFS (a) and OS (b) than those of the Other Patients Group
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4481300&req=5

Fig2: Kaplan–Meier survival curves on the correlation between favorable CTLA-4 expression profile and prognosis. Patients with high density CTLA-4+ interstitial lymphocytes (>33.44/mm2) and low CTLA-4 expression intensity in tumor cells (≤1.525) were characterized as the favorable CTLA-4 expression profile (FCEP) Group; the other patients were the Other Patients Group. Univariate analysis (log-rank) indicated that, the patients in FCEP group had longer DFS (a) and OS (b) than those of the Other Patients Group
Mentions: Based on the aforementioned analysis, we renamed Group 1 as the “favorable CTLA-4 expression profile” (FCEP) Group, and patients in Groups 2, 3 and 4 collectively as the “Other Patients” Group. The HER-2+ rate was significantly lower in the FCEP Group than in Other Patients Group (12.50 vs. 34.92 %, P = 0.048, Pearson Chi-square test). But the two groups did not significantly differ in other clinical features. Univariate analysis (log-rank) showed the DFS of FCEP Group (N = 43, events = 3, mean DFS = 133.332 months) was longer than DFS of Other Patients Group(N = 85, events = 30, mean DFS = 108.384 months; P < 0.001), and OS of FCEP Group (N = 43, events = 2, mean OS = 134.782 months) was longer than OS of Other Patients Group(N = 85, events = 27, mean OS = 111.471 months; P = 0.001) (Fig. 2). Multivariate analysis showed that (after controlling for age, clinical stage, SBR grade, tumor thrombus, ER, PR, HER2 and Ki-67) FCEP status independently predicted longer DFS (HR 0.148, 95 % CL 0.045–0.489, P = 0.002) and OS (HR 0.116, 95 % CL 0.027–0.495, P = 0.004). Clinical stage, SBR grade and HER-2 were also independent predictors of DFS and OS.Fig. 2

Bottom Line: Univariate analysis (log-rank) associated higher density of interstitial CTLA-4(+) lymphocytes with longer DFS and OS, but higher tumor CTLA-4 expression with shorter OS.These results indicated that CTLA-4 expression in lymphocytes was associated with better prognosis, but that in tumor cells was associated with worse prognosis.Patients' CTLA-4 profiles might thus be used to predict the benefits and toxicity of CTLA-4 blockade.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, General Hospital of Chinese People's Liberation Army, No. 28, Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China.

ABSTRACT
To examine the relationship between cytotoxic T lymphocyte antigen 4 (CTLA-4) expression and breast cancer prognosis, CTLA-4 expression was immunohistochemically detected in paraffin-embedded specimens of primary tumors from 130 patients with breast cancer who had a mean follow-up period of 112 months. CTLA-4 expressed in cytoplasm of breast cancer cells and in cytoplasm and cell membranes of interstitial lymphocytes. Univariate analysis (log-rank) associated higher density of interstitial CTLA-4(+) lymphocytes with longer DFS and OS, but higher tumor CTLA-4 expression with shorter OS. After controlling for age, clinical stage, Scarff-Bloom-Richardson grade, tumor thrombus, ER, PR, HER2 and Ki-67, multivariate analysis (Cox) showed that density of interstitial CTLA-4(+) lymphocytes independently predicted longer DFS (HR 0.315, P = 0.002) and OS (HR 0.313, P = 0.005), whereas tumor CTLA-4 expression independently predicted shorter DFS (HR 2.176, P = 0.029) and OS (HR 2.820, P = 0.007), i.e., patients with high CTLA-4(+) lymphocyte density and CTLA-4(low) tumor cells had the best prognoses. These results indicated that CTLA-4 expression in lymphocytes was associated with better prognosis, but that in tumor cells was associated with worse prognosis. Patients' CTLA-4 profiles might thus be used to predict the benefits and toxicity of CTLA-4 blockade.

Show MeSH
Related in: MedlinePlus