ABSTRACT
The epithelial-mesenchymal transition (EMT) contributes to the metastatic cascade in various tumors. C-C chemokine receptor 7 (CCR7) interacts with its ligand, chemokine (C-C motif) ligand 19 (CCL19), to promote EMT. However, the association between EMT and CCR7 in extrahepatic cholangiocarcinoma (EHCC) remains unknown. This study aimed to elucidate the prognostic impact of CCR7 expression and its association with clinicopathological features and EMT in EHCC. The association between CCR7 expression and clinicopathological features and EMT status was examined via the immunohistochemical staining of tumor sections from 181 patients with perihilar cholangiocarcinoma. This association was then investigated in TFK-1 and EGI-1 EHCC cell lines. High-grade CCR7 expression was significantly associated with a large number of tumor buds, low E-cadherin expression, and poor overall survival. TFK-1 showed CCR7 expression, and Western blotting revealed E-cadherin downregulation and vimentin upregulation in response to CCL19 treatment. The wound healing and Transwell invasion assays revealed that the activation of CCR7 by CCL19 enhanced the migration and invasion of TFK-1 cells, which were abrogated by a CCR7 antagonist. These results suggest that a high CCR7 expression is associated with an adverse postoperative prognosis via EMT induction and that CCR7 may be a potential target for adjuvant therapy in EHCC.
ABSTRACT
BACKGROUND/AIM: A subset of patients with estrogen receptor (ER)-positive, HER2-negative, and node-negative breast cancer experience recurrences. Predicting patients who will have recurrences within 5 years of surgery is essential so that patients can be selected to receive adjuvant chemotherapy. The 95-gene classifier (95-GC) has been validated as a method to differentiate patients into high and low-risk groups for early recurrence. PATIENTS AND METHODS: In this study, we performed 95-GC analysis on 56 formalin-fixed paraffin-embedded (FFPE) tissue samples from patients who underwent surgery for ER-positive, HER2-negative, and node-negative breast cancer and did not receive adjuvant chemotherapy. We associated the obtained high- and low-risk groups with clinicopathological characteristics and recurrence-free survival (RFS). RESULTS: We classified 12 out of 56 patients into the high-risk recurrence group. We found significantly higher KI67 scores in patients in the high-risk group. Other clinicopathological characteristics were not associated with the 95-GC risk groups. Patients in the 95-GC low-risk group had a significantly better prognosis than those in the high-risk group (p=0.0387). The 5-year RFS rate was 97.6% in the low-risk group and 74.1% in the high-risk group, while the 10-year RFS rates were 90.1% and 74.1%, respectively. CONCLUSION: The 95-GC score can accurately predict RFS within 5 years of surgery for ER-positive, HER2-negative, and node-negative breast cancer using FFPE tissue samples. These prediction models could help assign patients to the most effective treatment regimen.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Receptor, ErbB-2/genetics , Paraffin Embedding , Receptors, Estrogen , Neoplasm Recurrence, Local/pathology , Prognosis , Formaldehyde , Chemotherapy, AdjuvantABSTRACT
Mucin 1 (MUC1) expression is upregulated in multiple types of cancer, including lung cancer. However, the conventional anti-MUC1 antibody is not useful for the differentiation of malignant lung tumors and benign lesions due to its limited specificity. Our previous study screened a novel epitope-defined antibody against cancer-associated sugar chain structures that specifically recognizes the MUC1 Tn antigen (MUC1-Tn ED Ab). In the present study, its potential utility as a diagnostic marker and therapeutic tool for lung adenocarcinoma (ADC) was examined. Immunohistochemical analysis of a lung ADC tissue microarray was performed using the MUC1-Tn ED Ab (clone SN-102), and the results were compared with those of another clone and commercially available MUC1 antibodies. The association between positive immunoreactivity of SN-102 and clinicopathologic factors was analyzed. Furthermore, the association between MUC1-Tn expression and epithelial-mesenchymal transition markers and radiological characteristics was analyzed. Moderate or high MUC1-Tn expression (MUC1-Tn-H) was observed in 138 (78.9%) of the 175 lung ADC cases. MUC1-Tn-H was associated with male sex, cigarette smoking, tumor extension, pleural invasion, and higher preoperative serum carcinoembryonic antigen and cytokeratin 19 fragment levels. Tumors with MUC1-Tn-H had higher consolidation/tumor ratios according to computed tomography and greater uptakes of 18F-fluorodeoxyglucose. A total of 46 (26.9%) of the tumors had mesenchymal features, and MUC1-Tn positivity was higher in the mesenchymal group than in the epithelial and intermediate groups (P<0.01 and P<0.01, respectively). Patients with tumors exhibiting MUC1-Tn-H had significantly shorter 5-year overall and disease-free survival times (P=0.011 and P<0.001, respectively). Additionally, MUC1-Tn-H was identified as an independent prognostic factor in multivariate analysis (P=0.024). MUC1-Tn is specific for lung cancer cells and can improve diagnostic capabilities. Additionally, it may be a potential therapeutic target in lung ADC.