[Show abstract][Hide abstract] ABSTRACT: Few studies has documented early relapse in luminal B/HER2-negative breast cancer. We examined prognostic factors for early relapse among these patients to improve treatment decision-making.
PLoS ONE 03/2014; 9(8):e95629. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tumor-associated macrophages (TAMs) can promote cancer initiation and progression by releasing cytokines. Previously, we have found the density of TAMs correlated with lymph node metastasis in papillary thyroid carcinoma (PTC). However the mechanisms of how TAMs promote PTC progression remain unclear.In this study, we first showed that the TAMs density in the tumor core was associated with progressive PTC features and TAMs conditioned medium enhanced PTC cells invasion. Cytokine profiling identified a mixed M1/M2 phenotype and CXCL8 was the most consistently abundant cytokine in PTC-derived TAMs. CXCL8 receptors, CXCR1 and CXCR2, were positively stained in PTC cell lines and tissues, though no association with lymph node metastasis or extrathyroid extension. PTC cell invasion was abrogated by anti-CXCL8 neutralizing antibody, while addition of exogenous recombinant human CXCL8 enhanced the invasiveness. More importantly, CXCL8 promoted PTC metastasis in vivo. No difference was found for TAMs derived CXCL8 expression in patients with and without lymph node metastasis or extrathyroid extension. These findings indicated that TAMs may facilitate PTC cell metastasis through CXCL8 and its paracrine interaction with CXCR1/2.
[Show abstract][Hide abstract] ABSTRACT: The programmed death-1 (PD-1) molecule is mainly expressed on functionally "exhausted" CD8(+) T cells, dampening the host antitumor immune response. We evaluated the ratio between effective and regulatory T cells (Tregs) and PD-1 expression as a prognostic factor for operable breast cancer patients. A series of 218 newly diagnosed invasive breast cancer patients who had undergone primary surgery at Ruijin Hospital were identified. The influence of CD8(+) cytotoxic T lymphocytes, FOXP3(+) (Treg cell marker), and PD-1(+) immune cell counts on prognosis was analyzed utilizing immunohistochemistry. Both PD-1(+) immune cells and FOXP3(+) Tregs counts were significantly associated with unfavorable prognostic factors. In bivariate, but not multivariate analysis, high tumor infiltrating PD-1(+) cell counts correlated with significantly shorter patient survival. Our results suggest a prognostic value of the PD-1(+) immune cell population in such breast cancer patients. Targeting the PD-1 pathway may be a feasible approach to treating patients with breast cancer.
Cancer Immunology and Immunotherapy 02/2014; · 3.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The chromodomain helicase/adenosine triphosphatase DNA binding protein 1-like gene (CHD1L) is a recently identified oncogene localized at 1q21. CHD1L protein over-expression in primary hepatocellular carcinoma is correlated with enhanced apoptosis inhibition, reduced chemosensitivity and shortened patient survival. However, CHD1L protein status or mRNA expression in breast cancer and its clinical significance remain obscure.
PLoS ONE 01/2014; 9(8):e98673. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki67 have been increasingly evaluated by core needle biopsy (CNB) and are recommended for classifying breast cancer into molecular subtypes. However, the concordance rate between CNB and open excision biopsy (OEB) has not been well documented.
Patients with paired CNB and OEB samples from Oct. 2009 to Feb. 2012 in Ruijin Hospital were included. ER, PgR, HER2, and Ki67 were determined by immunohistochemistry (IHC). Patients with HER2 IHC 2+ were further examined by FISH. Cutoff value for Ki67 high expression was 14%. Molecular subtypes were constructed as follows: Luminal A, Luminal B, Triple Negative, and HER2 positive.
There were 298 invasive breast cancer patients analyzed. Concordance rates for ER, PgR, and HER2 were 93.6%, 85.9%, and 96.3%, respectively. Ki67 expression was slightly higher in OEB than in CNB samples (29.3% vs. 26.8%, P = 0.046). Good agreement (kappa = 0.658) was demonstrated in evaluating molecular subtypes between CNB and OEB, with a concordance rate of 77.2%. We also used a different Ki67 cutoff value (20%) for determining Luminal A and B subtypes in HR (hormone receptor) +/HER2- diseases and the overall concordance rate was 79.2%. However, using a cut-point of Ki67 either 14% or 20% for both specimens, there will be about 14% of HR+/HER2- specimens that are called Luminal A on CNB and Luminal B on OEB.
CNB was accurate in determining ER, PgR, and HER2 status as well as non-Luminal molecular subtypes in invasive breast cancer. Ki67 should be retested on OEB samples in HR+/HER2- patients to accurately distinguish Luminal A from B tumors.
BMC Cancer 08/2013; 13(1):390. · 3.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Tumor associated macrophages (TAMs) have recently been recognized as an important player in the tumoriogenesis of many cancers, including advanced thyroid cancer. However, a role in papillary thyroid carcinoma (PTC), the most prevalent thyroid cancer, has not been established. We hypothesized that TAMs facilitate tumor progression in PTC as well. Methods We investigated TAMs density in both benign thyroid lesions and PTC tumors by CD68 immunostaining. CD68 positive cell density was further associated with clinicopathological characters of PTC patients. Finally, TAMs were isolated from PTC tumors and phenotyped it by cytokine and receptor profiling. Results The overall density of TAMs was found to be significantly higher in PTC tumors, compared with thyroid goiter and follicular adenoma (FA). TAMs density was positively associated with lymph node metastasis and TNM stages III/VI compared with Stages I/II. No association was observed other common tumor features, including BRAF mutation. The isolated TAMs presented with high levels of M2 associated cytokine and receptors, making M2 the predominant TAM phenotype. Conclusions TAMs may have a functional role in the progression of PTC tumors.
Thyroid: official journal of the American Thyroid Association 05/2012; · 2.60 Impact Factor