TGF-β1 precursor and CD8 are potential prognostic and predictive markers in operated breast cancer.
10.1007/s11596-014-1231-2
- Author:
Hai-ming YU
1
;
Jun-lan YANG
;
Shun-chang JIAO
;
Jian-dong WANG
;
Ying LI
Author Information
1. Department of Medical Oncology, General Hospital of Chinese People's Liberation Army, Beijing, 100853, China, 905875019@qq.com.
- Publication Type:Journal Article
- MeSH:
Biomarkers, Tumor;
metabolism;
Breast Neoplasms;
drug therapy;
metabolism;
surgery;
CD8-Positive T-Lymphocytes;
metabolism;
Chemotherapy, Adjuvant;
Combined Modality Therapy;
Female;
Humans;
Immunohistochemistry;
Kaplan-Meier Estimate;
Middle Aged;
Outcome Assessment (Health Care);
methods;
statistics & numerical data;
Prognosis;
Proportional Hazards Models;
Protein Precursors;
metabolism;
Retrospective Studies;
Transforming Growth Factor beta1;
metabolism
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2014;34(1):51-58
- CountryChina
- Language:English
-
Abstract:
The transforming growth factor β1 (TGF-β1) and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130 (stage I-III) invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival (DDFS) (HR=8.416, 95% CI=1.636-43.292, P=0.011) in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival (OS) than their counterparts with CD8-positive cell infiltration into tumor nests (Log-Rank, P=0.003). But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy (Log-Rank, P=0.013) and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor (t-TGF-β1-pre)-positive patients than in the negative patients in patients without receiving chemotherapy (P=0.053), OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy (P=0.035) and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS (HR=0.392 95% CI=0.157-0.978, P=0.045) in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.
