Tumor Budding in Breast Carcinoma: Relation to E-Cadherin, MMP-9 Expression, and Metastasis Risk

Abstract

Background: Tumor budding is a histopathologic entity refers to small cluster of cancer cells at the invasive edge of tumor. It was assumed that tumor budding is linked to epithelial-mesenchymal transition, an early event in metastasis. Objective: This study aimed to find out the correlation of tumor budding with E-cadherin and MMP-9 expression and risk of metastasis in breast carcinoma. Method: We investigated 35 cases breast carcinoma with metastasis and 35 cases without metastasis. The number of tumor budding was counted in cytokeratin-stained slides with 400x magnification (0.57 mm 2 ).Result: Cut-off point by ROC analysis was 11 and the patient was categorized into low grade (0-10 buds) and high grade (11 or more buds) tumor budding. Inter-observer agreement was good with K value 0.914. Low level of E-cadherin was not significantly correlated with high grade tumor budding (p=0.660), meanwhile high level of MMP-9 was significantly correlated with high grade tumor budding (p=0.001). High grade tumor budding was a significant, independent risk factor of metastasis in breast carcinoma (OR=38.2, 95% CI 7. 5-193.7, p<0.001). Conclusion:In conclusion, tumor budding grade is related to level of MMP-9 but has no correlation E-cadherin expression. High grade tumor budding is an independent risk factor of metastasis in breast carcinoma.

A Retrospective Study of Association of Tumor Budding, Tumor Microenvironment, and Clinicopathological Characteristics of Invasive Breast Carcinoma

“…In the present study, PTB did not show any significant association with age of patients, tumor size, and the overall histological grade. This finding was similar to KumarGuru et al, 16 Gujam et al, 7 and Salhia et al 6 However, Sriwidyani et al 17 observed significant association of PTB with histological grade, while Liang et al 2 found a significant association of tumor size with PTB ( Table 4 ).…”

The Correlation of Tumor Budding Index with Clinicopathology Parameters on Invasive Breast Carcinoma No Special Type

“…The results of this study are in line with research conducted by Sriwidayani et al in 2016, where they found LVI as much as 75.71%. 49 Whereas, in research conducted by Renuka et al in 2019 found LVI as much as 74%. 54 After statistical test analysis, a significant association was found between the tumor budding index and LVI in this study.…”

“…52 Sriwidyani et al in 2016 found that the average age of patients aged 48.6 years with an age range in his study of 23-74 years. 49 Kumarguru et al in 2020 found that the average age of patients is 53.14 years, with an age range of 24-77 years. 48 This study found that the age of breast carcinoma sufferers is at an advanced age that occurs in women over 50 years.…”

“…52 Research by Sriwidyani et al in 2016 also obtained results in line where grading is most found in grade 3 as much as 50%. 49 Agarwal et al in 2019 reported that the most common grade 3 cases were 82%. 17 This is likely due to lack of awareness people to do early detection so that breast carcinoma is found at a high grade.…”

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“…Breast cancer treatment intricately hinges on the evaluation of predictive markers and pathological insights, forming the foundation for patient-centered decisions and therapeutic strategies. Particularly within the context of early-stage breast cancer, where tailored systemic interventions mandate personalized considerations, three cardinal prognostic factors take precedence in routine clinical practice: lymph node status, tumor dimensions, and histological grade [28][29][30]. Notably, the Histological Grade (HG) of the tumor emerges as a paramount anatomical attribute.…”