BackgroundExtracellular matrix protein 1 (ECM1) and vascular endothelial growth factor-C (VEGF-C) are secretory glycoproteins that are associated with lymphangiogenesis; these proteins could, therefore, play important roles in the lymphatic dissemination of tumors. However, very little is known about their potential roles in lymphangiogenesis. The aim of this study was to investigate whether correlations exist between ECM1 and VEGF-C in human breast cancer, lymphangiogenesis, and the clinicopathological characteristics of the disease.MethodsECM1 and VEGF-C mRNA and protein expression levels in 41 patients were investigated using real-time reverse transcriptase polymerase chain reaction (RT-PCR), or immunohistochemical (IHC) staining of breast cancer tissue, matched noncancerous breast epithelial tissues, and suspicious metastatic axillary lymph nodes. D2-40 labelled lymph vessels and lymphatic microvessel density (LMVD) were counted. Correlations between ECM1 or VEGF-C protein expression levels, LMVD, and clinicopathological parameters were statistically tested.ResultsThe rate of ECM1 positive staining in breast cancer tissues was higher (31/41, 75.6%) than that in the corresponding epithelial tissues (4/41, 9.8%, P < 0.001) and lymph nodes (13/41, 31.7%, P < 0.001). Similarly, the VEGF-C expression rate in cancer specimens was higher (33/41, 80.5%) than in epithelial tissues (19/41, 46.3%, P < 0.01) or lymph nodes (15/41, 36.6%, P < 0.01). Higher ECM1 and VEGF-C mRNA expression levels were also detected in the tumor tissues, compared to the non-cancerous tissue types or lymph nodes (P < 0.05). ECM1 protein expression was positively correlated with the estrogen receptor status (P < 0.05) and LMVD (P < 0.05). LMVD in the ECM1- and VEGF-C-positive tumor specimens was higher than that in the tissue types with negative staining (P < 0.05).ConclusionsBoth ECM1 and VEGF-C were overexpressed in breast cancer tissue samples. ECM1 expression was positively correlated with estrogen responsiveness and the metastatic properties of breast cancer. We conclude, therefore, that ECM1 and VEGF-C may have a synergistic effect on lymphangiogenesis to facilitate lymphatic metastasis of breast cancer.
BackgroundMatrix metalloproteinase 9 (MMP-9) is a type-IV collagenase that is highly expressed in breast cancer, but its exact role in tumor progression and metastasis is unclear.Methods
MMP-9 mRNA and protein expression was examined by real-time reverse transcriptase PCR and immunohistochemical staining, respectively, in 41 breast cancer specimens with matched peritumoral benign breast epithelial tissue and suspicious metastatic axillary lymph nodes. Lymph vessels were labeled with D2-40 and lymphatic microvessel density (LMVD) was calculated. Correlation of MMP-9 protein expression with clinicopathological parameters and LMVD was also evaluated.ResultsMMP-9+ staining in breast cancer specimens (35/41, 85.4%) was higher than in matched epithelium (21/41, 51.2%; P<0.05) and lymph nodes (13/41, 31.7%; P<0.001). Higher MMP-9 mRNA expression was also detected in tumor specimens compared with matched epithelial tissues and lymph nodes (P<0.05). Elevated MMP-9 expression was correlated with lymph node metastasis and LMVD (P<0.05).ConclusionMMP-9 was overexpressed in breast cancer specimens compared with peritumoral benign breast epithelium and lymph nodes. Moreover, its expression in the matched epithelium and lymph nodes was positively associated with lymph node metastasis, and its expression in lymph nodes was positively associated with lymphangiogenesis in breast cancer. Thus, MMP-9 is a potential marker for breast cancer progression.
Background: Palbociclib is the most widely used cyclin-dependent kinase 4/6 inhibitor in China, but its early application efficacy on Chinese metastatic breast cancer (MBC) patients was reported deficiently. Methods: Between February 2019 to December 2021, 95 female hormone receptor-positive (HR+)/human epidermal growth factor receptor-2 negative (HER2−) patients with MBC received palbociclib combined with AI or fulvestrant were retrospectively analyzed in our center. The primary outcome was progression-free survival (PFS). The objective response rate and clinical benefit rate (CBR) were evaluated. Results: The median follow-up period was 15 months (range from 2 to 37). Palbociclib performed superiorly when applicated in first-and-second line therapy than in later lines ( P = .002). Palbociclib combined with AI or fulvestrant had a median PFS of 34 months (95% confidence interval [CI] = 6.87-61.13) and 12 months (95%CI = 7.76-16.24), respectively. Univariate subgroup analysis showed that the previous history of salvage chemotherapy ( P = .015) and the presence of liver metastases ( P < .001) significantly affected the efficacy of palbociclib. Despite the existence of liver metastases and primary endocrine resistance, which are two independent predictors of poor prognosis, early application of palbociclib in advanced stage can bring further benefits to these two groups of patients, rather than choosing salvage chemotherapy in the first place. Conclusion: Palbociclib combined with endocrine therapy has a favorable efficacy and acceptable toxicity in HR+/HER2− Chinese MBC patients. Better performance can be seen when palbociclib was applicated in the early stage.
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