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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: 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.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.

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Related in: MedlinePlus

Expression profiles of CTLA-4 in breast cancer. CTLA-4 was expressed in cytoplasm and cell membrane of interstitial lymphocytes (a); CTLA-4+ cytoplasmic dots were found in cytoplasm of tumor cells (b)
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Fig1: Expression profiles of CTLA-4 in breast cancer. CTLA-4 was expressed in cytoplasm and cell membrane of interstitial lymphocytes (a); CTLA-4+ cytoplasmic dots were found in cytoplasm of tumor cells (b)

Mentions: CTLA-4 was expressed in cytoplasm and cell membrane of interstitial lymphocytes (Fig. 1a); CTLA-4+ discrete cytoplasmic dots were found in cytoplasm of tumor cells (Fig. 1b). The optimal OS cutoff value for tumor CTLA-4 expression was 1.525 (sensitivity: 51.7 %; specificity: 67.3 %; area under curve [AUC]: 0.537; SE = 0.069) and for density of interstitial CTLA-4+ lymphocytes was 33.44/mm2 (sensitivity: 63.4 %; specificity: 69 %; AUC: 0.695; SE = 0.058) (ROC curves see Supplementary Figure 3).Fig. 1


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)

Expression profiles of CTLA-4 in breast cancer. CTLA-4 was expressed in cytoplasm and cell membrane of interstitial lymphocytes (a); CTLA-4+ cytoplasmic dots were found in cytoplasm of tumor cells (b)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Expression profiles of CTLA-4 in breast cancer. CTLA-4 was expressed in cytoplasm and cell membrane of interstitial lymphocytes (a); CTLA-4+ cytoplasmic dots were found in cytoplasm of tumor cells (b)
Mentions: CTLA-4 was expressed in cytoplasm and cell membrane of interstitial lymphocytes (Fig. 1a); CTLA-4+ discrete cytoplasmic dots were found in cytoplasm of tumor cells (Fig. 1b). The optimal OS cutoff value for tumor CTLA-4 expression was 1.525 (sensitivity: 51.7 %; specificity: 67.3 %; area under curve [AUC]: 0.537; SE = 0.069) and for density of interstitial CTLA-4+ lymphocytes was 33.44/mm2 (sensitivity: 63.4 %; specificity: 69 %; AUC: 0.695; SE = 0.058) (ROC curves see Supplementary Figure 3).Fig. 1

Bottom Line: 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.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