Purpose
Breast carcinomas, including basal and hereditary cases, often present with a prominent tumoral lymphocytic infiltrate (LI). Chemokines could play a role in attracting these cells and contribute to tumor progression. We explored tumoral expression of CXCL10 and determined the relationship between CXCL10 and LI in a cohort of breast cancers.
Experimental Design
Using tissue microarrays of 364 breast tumors we evaluated expression of CXCL10 and its receptor, CXCR3, in relation to histopathologic features, biomarkers and lymphocyte markers. Additionally, we overexpressed CXCL10 and CXCR3 in MCF7 breast cancer cells and monitored T-lymphocyte migration and invasion.
Results
Forty-five percent of tumors expressed CXCL10 and a significant association was found with CXCR3 and LI. Further characterization of the LI revealed an association with CXCL10 expression for peritumoral CD4+ and CD8+ lymphocytes. CD8+ intratumoral lymphocytes, FOXP3+ Tregs and T-BET+ Th1 cells were associated with BRCA1 and basal tumors. Conditioned media from MCF7 cells overexpressing both CXCL10 and CXCR3 increased T-lymphocyte migration and invasion.
Conclusions
Our findings suggest that CXCL10 may act in a paracrine manner, affecting the tumor microenvironment, and in an autocrine manner, acting on the tumor cells themselves and may play a role in tumor invasiveness and progression. The CXCL10-CXCR3 axis can serve as a potential target in BRCA1 and basal breast cancers which present with a prominent LI and a poor prognosis.
The objectives of this study were to determine the prognostic significance of subgrouping estrogen receptor (ER)-positive breast tumors into low-and high-risk luminal categories using Ki67 index, TP53, or progesterone receptor (PR) status. The study group comprised 540 patients with lymph node negative, invasive breast carcinoma. Luminal A subtype was defined as being ER positive, HER2 negative, and Ki67 low (o14% cells positive) and luminal B subtype as being ER positive, HER2 negative, and Ki67 high (Z14% cells positive). Luminal tumors were also subgrouped into risk categories based on the PR and TP53 status. Survival analysis was performed. Patients with luminal B tumors (n ¼ 173) had significantly worse disease-free survival compared to those with luminal A tumors (n ¼ 186) (log rank P-value ¼ 0.0164; univariate Cox regression relative risk 2.00; 95% CI, 1.12-3.58; P ¼ 0.0187). Luminal subtype remained an independent prognostic indicator on multivariate analysis including traditional prognostic factors (relative risk 2.12; 95% CI, 1.16-3.88; P ¼ 0.0151). Using TP53 status or PR negativity rather than Ki67 to classify ER-positive luminal tumors gave similar outcome results to those obtained using the proliferation index. However, it was a combination of the three markers, which proved the most powerful prognostically. Ki67 index, TP53 status, or PR negativity can be used to segregate ERpositive, HER2-negative tumors into prognostically meaningful subgroups with significantly different clinical outcomes. These biomarkers particularly in combination may potentially be used clinically to guide patient management.
The presence of ECS appears to be associated with survival in OPSCC and CUP according to p16 status. Our findings raise questions regarding the benefits of postoperative chemoradiation therapy in p16-positive patients with ECS.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.