Urokinase type plasminogen activator receptor (uPAR) and human epidermal growth factor receptor 2 (HER2) expression in metastasis of breast cancer.

BACKGROUND: The plasminogen urokinase activation system consists of urokinase plasminogen activator (uPA), its receptor uPAR, and plasminogen activator inhibitor type 1 (PAI-1), which are considered to have a relationship with cancer aggressiveness. Several studies have found correlations between HER2 mRNA and uPAR in disseminated tumor cells (DTCs) in breast cancer patients. They are associated with a more aggressive primary tumor phenotype and recurrence/metastasis. OBJECTIVE: This study aims to determine the relationship between the expression of urokinase-type plasminogen activator receptor (uPAR) and human epidermal growth factor receptor type 2 (HER2) with the incidence of distant metastases in breast cancer. METHODS: This study was an observational study using a cross-sectional method and was conducted at Wahidin Sudirohusodo Hospital and the network. Immunohistochemical methods carry out examination of uPAR and HER2 expression from tissues of breast cancer patients. The relationship of uPAR, HER2 expression, and metastasis was tested with the Mann Whitney test. RESULTS: The study results found that the proportion of patients with metastasis was significantly higher in high uPAR expression compared to low uPAR (77.8% compared to 36.8%). The negative HER2 expression was significantly higher in the low uPAR expression than the high uPAR (78.9% compared to 33.3%). In comparison, the positive HER2 expression was significantly higher in the high uPAR expression than the low uPAR (66.7% compared to 21.1%). In positive HER2 expression, the mean percentage of uPAR expression was significantly higher in metastases than those without metastasis (72.7% compared to 42.1%). CONCLUSIONS: uPAR expression is associated with metastasis in HER2 positive breast cancer.

The expression of programmed death-ligand 1 and its association with histopathological grade, stage of disease, and occurrence of metastasis in breast cancer.

INTRODUCTION: Programmed death ligand 1 (PD-L1) plays a role in tumor escape and progression by inactivating T lymphocytes. The aim of the study reported here was to determine the relationship between the expression of PD-L1 and histopathological grade, stage of disease, and the occurrence of metastasis in breast cancer. METHODS: The observational cross-sectional study involved analyzing the expression of PD-L1 by immunohistochemistry. RESULTS: PD-LI was expressed in 43 of 60 patients with breast cancer (71.6%), mostly with a moderate histopathological grade (58.3%) and at an advanced stage (50%). Associations between the expression of PD-L1 and histopathological grade (p = 0.011), stage of disease (p = 0.009), and the occurrence of metastasis (p = 0.01) were significant, with an odds ratio of 5. CONCLUSION: The associations between the expression of PD-L1 and histopathological grade, disease stage, and occurrence of metastasis were all significant in cases of breast cancer in the sample. Those findings suggest that the expression of PD-L1 increases the progression of breast cancer.

Association of ERα-36 expression with the de novo resistance of tamoxifen in ER-positive breast cancer.

BACKGROUND: Approximately 70-80% of breast cancer express ER-alpha and hormonal therapies, given significant improvements in patient survival. About 50% of ER-positive breast cancer patients with advanced disease insensitive to tamoxifen treatment when diagnosed. Recent studies have shown that ERα-36 is a crucial factor in the resistance of tamoxifen. OBJECTIVE: This study aims to determine the association between ERα-36 expression and de novo resistance of tamoxifen in patients with ER-positive breast cancer. METHODS: This study was an observational study using a cross-sectional method and was conducted at Wahidin Sudirohusodo Hospital and Unhas Hospital. ERα-36 protein expression was assessed using an immunohistochemistry assay. The association of ERα-36 expression and resistance of tamoxifen was tested with the Chi-square test. RESULTS: A total of 50 locally advanced breast cancer cases were included in this study, 22 cases (44%) had overexpression of ERα-36, and 28 cases (56%) had not, 24 cases (48%) had experience resistance to tamoxifen and 26 cases (52%) had not. There was a significant association between ERα-36 expressions and resistance of tamoxifen (p = 0.000). CONCLUSIONS: There was an association between the expression of ER-α36 with de novo resistance of tamoxifen in ER-positive breast cancer. ER-α36 could act as a worth considering biomarker for de novo resistance of tamoxifen in therapeutic strategies.