Search

ObjectiveTo investigate the expression of CD117 and DOG1 in triple-negative breast cancer (TNBC) and to explore their relationship with clinicopathologic features and prognosis.MethodsThe patients with TNBC in Peking Union Medical College Hospital from 2000 to 2011 were retrospectively collected and tissue microarrays were made. The expression of CD117 and DOG1 in tumor cells was detected by immunohistochemistry to analyze their relationship with the clinicopathological characteristics of the patients, such as age, tumor diameter, American Joint Committee on Cancer (AJCC) cancer stage, histological grade, P53, and Ki-67 proliferation index, and explore the effect of both on the survival of patients.ResultsA total of 185 TNBC patients meeting the inclusion and exclusion criteria were selected, of which 24 (12.97%) were CD117 positive and 22 (11.89%) were DOG1 positive, with a co-expression rate of 1.62%. Compared with CD117-negative patients, CD117-positive patients had higher Ki-67 proliferation index (87.50% vs. 67.70%, P=0.048), basal-like TNBC (95.83% vs. 74.53%, P=0.020), and P53 diffuse positive (33.33% vs. 13.66%, P=0.032).Compared with DOG1-negative patients, DOG1-positive patients had lower proportions of tumor diameter ≤2 cm (22.73% vs. 45.40%, P=0.026) and basal-like TNBC (54.55% vs. 80.37%, P=0.015). The median follow-up was 71 months (range: 2-170 months), 4 cases (2.16%) were lost to follow-up, 66 cases (35.68%) relapsed or had distant metastasis, and 34 cases (18.38%) died. Survival analysis showed that AJCC stage (HR=7.624, 95% CI: 2.187-26.576, P=0.001) and CD117 positive with P53 diffuse strong positive (HR=3.942, 95% CI: 1.366-11.379, P=0.011) were negatively correlated with the overall survival of TNBC patients.ConclusionsThe expression of CD117 and DOG1 were significantly related to basal-like TNBC, CD117 positive with P53 diffuse strong positive may be correlated with a shorter overall survival and a higher mortality risk.

V-domain Ig suppressor of T-cell activation (VISTA), a newly discovered negative immune checkpoint, is thought to be related to immunotherapy resistance and may become a new immune therapeutic target. Here, we evaluated the expression of VISTA in a cohort containing 254 patients with untreated triple-negative breast cancer. The relevance of VISTA expression, clinicopathologic parameters, expression of other immune markers, and prognosis were investigated in the whole cohort. Genomic analysis of 139 triple-negative breast cancer (TNBC) patients from the cancer genome atlas (TCGA) was also performed. VISTA was expressed in the immune cells (ICs) and in the tumor cells (TCs) in 87.8% (223/254) and 18.5% (47/254) of the cohort, respectively. VISTA-positive ICs were associated with no lymph node metastasis (p < 0.001), American Joint Committee on Cancer (AJCC) stage I and II (p = 0.001) and basal-like subtype (p < 0.001). VISTA expression in ICs positively correlated with some tumor-infiltrating lymphocytes (TILs) types, particularly with the CD4+TILs, which was consistent with mRNA level analysis from the TCGA database. Survival analysis showed that patients with VISTA-positive ICs had prolonged relapse-free and overall survival compared with the negative ones, especially among T1-2N0 stage patients. Multivariate analysis showed that it independently predicted the prognosis. These data confirmed the regulatory role of VISTA in anti-tumor immunity, changed our perception of VISTA as a negative immune checkpoint, and suggested VISTA as a potential therapeutic target for TNBC. [ABSTRACT FROM AUTHOR]

Background: The BRAF V600E and telomerase reverse transcriptase (TERT) promoter mutations have been reported in papillary thyroid carcinoma (PTC). The aim of this retrospective cross-sectional study was to add further information regarding the prevalence of the BRAF V600E and TERT promoter mutations in Chinese PTC and their clinicopathological associations. Methods: We detected the BRAF V600E mutation and TERT promoter mutations in 455 Chinese PTC patients and analyzed the association of these mutations with several clinicopathological features. Results: The BRAF V600E mutation was detected in 343 (75.4%) of 455 cases and was significantly associated with older age (p<0.001) and conventional subtype (p = 0.003). TERT promoter mutations were detected in 19 (4.4%) of 434 PTCs and were associated with older age (p<0.001), larger tumor size (p = 0.024), and advanced TNM stage(p<0.001). Of the 19 patients that were positive for TERT promoter mutations, 18 (94.7%) also harbored the BRAF V600E mutation. Conclusion: We determined the prevalence and clinicopathological associations of BRAF V600E and TERT promoter mutations in Chinese PTC patients. TERT promoter mutations but not the BRAF V600E mutation were associated with more advanced TNM stage upon diagnosis. [ABSTRACT FROM AUTHOR]