scholarly journals Lymphangiogenesis in breast carcinoma is present but insufficient for metastatic spread

2014 ◽  
Vol 4 (1) ◽  
pp. 4-11
Author(s):  
Mirsad Dorić ◽  
Suada Kuskunović-Vlahovljak ◽  
Svjetlana Radović ◽  
Ajna Hukić ◽  
Mirsad Babić ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Breast Carcinoma ◽  
Histological Grade ◽  
Lymphatic Vessels ◽  
Lymphatic Endothelial Cell ◽  
Breast Disease ◽  
Invasive Breast Carcinoma ◽  
Endothelial Cell Proliferation ◽  
Fibrocystic Breast Disease

Introduction: The lymphatic vasculature is an important route for the metastatic spread of human cancer. However, the extent to which this depends on lymphangiogenesis or on invasion of existing lymph vessels remains controversial. The goal of this study was to investigate the existence of lymphangiogenesis in invasive breast carcinoma: by measuring the lymphatic vessels density (LVD) and lymphatic endothelial cell proliferation (LECP) and their correlation with various prognostic parameters in breast cancer, including lymphovascular invasion (LVI).Methods: Lymphatic vessels density was investigated in 75 specimens of invasive breast carcinoma by immunostaining for D2-40 using the Chalkley counting method. Endothelial proliferation in lymphatic vessels was analyzed by dual-color immunohistochemistry with D2-40 and Ki-67.Results: Decrease of intra and peritumoral LVD in invasive breast carcinoma compared to fibrocystic breast disease was detected (p=0.002). Lymphatic endothelial cell proliferation was significantly higher in invasive breast cancer (p=0.008) than in the fibrocystic breast disease. LECP showed a correlation with histological grade of the tumor (p=0.05). Involvement of axillary lymph nodes with metastatic tissue was in strong correlation only with existence of lymphatic vascular invasion (p=0.0001).Conclusion: These results suggest that development of breast cancer promotes proliferation of lymphatic endothelial cells whose level correlates with histological grade of tumor, but in a scope that is insufficient to follow growth of tumor tissue that invades them and destruct them. This might explain the decrease of lymphatic vessels density.

CLINICAL AND HISTOPATHOLOGICAL REVIEW OF INVASIVE BREAST CARCINOMA IN A TERITARY CARE CENTRE.

2021 ◽  
pp. 18-21
Author(s):  
A. Gomathy ◽  
Muruganantham Arunagirinathan ◽  
I. Nithya
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Cancer Survival ◽  
Histological Grade ◽  
Lymph Node Involvement ◽  
Left Breast ◽  
Invasive Breast Carcinoma ◽  
Indian Women ◽  
Node Involvement ◽  
Grade Ii

BACKGROUND: Breast cancer accounts for 14% of all cancers in Indian women, that can occur at any age. Cancer survival becomes more difcult in higher stages of tumour, hence in order to improve the survival of affected persons, early diagnosis of breast cancer is critical. METHODS: Retrospective study of 48 mastectomy specimens with relevant clinical details and respective H&E stained slides were reviewed. CONCLUSION: This review showed that occurrence of Invasive Breast Carcinoma(IBC) peaks in the age group of 41-50years (35.4% ) with right and left breast being affected equally in the ratio of R:L – 1 : 1. Most of the IBC (91.6%) were of No Special Type (NST), with 75% of tumours were of Histological Grade II. 58.3% of tumours were of tumour stage T along with lymph node involvement in equal number of cases.

scholarly journals Sonic hedgehog selectively promotes lymphangiogenesis after kidney injury through noncanonical pathway

2019 ◽  
Vol 317 (4) ◽  
pp. F1022-F1033 ◽  
Author(s):  
Hui Zhuo ◽  
Dong Zhou ◽  
Yuanyuan Wang ◽  
Hongyan Mo ◽  
Ying Yu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Sonic Hedgehog ◽  
Lymphatic Vessels ◽  
Kidney Injury ◽  
Lymphatic Endothelial Cell ◽  
Cell Counting ◽  
Endothelial Cell Proliferation ◽  
Vascular Endothelial

Kidney fibrosis is associated with an increased lymphangiogenesis, characterized by the formation and expansion of new lymphatic vessels. However, the trigger and underlying mechanism responsible for the growth of lymphatic vessels in diseased kidney remain poorly defined. Here, we report that tubule-derived sonic hedgehog (Shh) ligand is a novel lymphangiogenic factor that plays a crucial role in mediating lymphatic endothelial cell proliferation and expansion. Shh was induced in renal tubular epithelium in various models of fibrotic chronic kidney disease, and this was accompanied by an expansion of lymphatic vessels in adjacent areas. In vitro, Shh selectively promoted the proliferation of human dermal lymphatic endothelial cells (HDLECs) but not human umbilical vein endothelial cells, as assessed by cell counting, MTT assay, and bromodeoxyuridine incorporation. Shh also induced the expression of vascular endothelial growth factor receptor-3, cyclin D1, and proliferating cell nuclear antigen in HDLECs. Shh did not affect the expression of Gli1, the downstream target and readout of canonical hedgehog signaling, but activated ERK-1/2 in HDLECs. Inhibition of Smoothened with small-molecule inhibitor or blockade of ERK-1/2 activation abolished the lymphatic endothelial cell proliferation induced by Shh. In vivo, inhibition of Smoothened also repressed lymphangiogenesis and attenuated renal fibrosis. This study identifies Shh as a novel mitogen that selectively promotes lymphatic, but not vascular, endothelial cell proliferation and suggests that tubule-derived Shh plays an essential role in mediating lymphangiogenesis after kidney injury.

scholarly journals AN ASSESSMENT OF ANGIOGENESIS IN FIBROCYSTIC BREAST DISEASE AND INVASIVE BREAST CARCINOMA

2017 ◽  
Vol 6 (78) ◽  
pp. 5553-5556
Author(s):  
Duraisamy Raman ◽  
Sudha Boj ◽  
Dhanalakshmi Arumugam ◽  
Lalitha Chidambaram
Keyword(s):  
Breast Carcinoma ◽  
Breast Disease ◽  
Invasive Breast Carcinoma ◽  
Fibrocystic Breast Disease

scholarly journals Tumor collagen framework from bright-field histology images predicts overall survival of breast carcinoma patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mindaugas Morkunas ◽  
Dovile Zilenaite ◽  
Aida Laurinaviciene ◽  
Povilas Treigys ◽  
Arvydas Laurinavicius
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Cancer Patient ◽  
Breast Cancer Patient ◽  
Cox Regression ◽  
Regional Lymph Node ◽  
Histological Grade ◽  
Biological Information ◽  
Lymph Node Status ◽  
Bright Field

AbstractWithin the tumor microenvironment, specifically aligned collagen has been shown to stimulate tumor progression by directing the migration of metastatic cells along its structural framework. Tumor-associated collagen signatures (TACS) have been linked to breast cancer patient outcome. Robust and affordable methods for assessing biological information contained in collagen architecture need to be developed. We have developed a novel artificial neural network (ANN) based approach for tumor collagen segmentation from bright-field histology images and have tested it on a set of tissue microarray sections from early hormone receptor-positive invasive ductal breast carcinoma stained with Sirius Red (1 core per patient, n = 92). We designed and trained ANNs on sets of differently annotated image patches to segment collagen fibers and extracted 37 features of collagen fiber morphometry, density, orientation, texture, and fractal characteristics in the entire cohort. Independent instances of ANN models trained on highly differing annotations produced reasonably concordant collagen segmentation masks and allowed reliable prognostic Cox regression models (with likelihood ratios 14.11–22.99, at p-value < 0.05) superior to conventional clinical parameters (size of the primary tumor (T), regional lymph node status (N), histological grade (G), and patient age). Additionally, we noted statistically significant differences of collagen features between tumor grade groups, and the factor analysis revealed features resembling the TACS concept. Our proposed method offers collagen framework segmentation from bright-field histology images and provides novel image-based features for better breast cancer patient prognostication.

The value of tumor-infiltrating lymphocytes and CD8 expression as a predictor of response to anthracycline-based neoadjuvant chemotherapy in invasive breast carcinoma of no special type

2021 ◽  
pp. 1-6
Author(s):  
Upik A. Miskad ◽  
Rizki A. Rifai ◽  
Rina Masadah ◽  
Berti Nelwan ◽  
Djumadi Ahmad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Breast Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Predictive Value ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Invasive Breast Carcinoma ◽  
Study Results ◽  
Infiltrating Lymphocytes

BACKGROUND: The immune system is known to play an important role in tumor cell eradication. Although cancer cells were able to escape from the immune system, many studies showed mononuclear inflammatory cell infiltrates known as tumor-infiltrating lymphocytes (TILs) on breast cancer histopathology specimens showed better prognosis, including in disease-free survival (DFS) and chemotherapy responses. OBJECTIVE: This study aimed to reveal the predictive value of tumor-infiltrating lymphocytes (TILs) levels and CD8 expression in invasive breast carcinoma of no special type patients’ samples on response to anthracycline-based neoadjuvant chemotherapy. METHODS: 75 pre-treatment biopsy samples that were diagnosed as invasive breast carcinoma of no special type were evaluated. TILs level determined following recommendations of International TILs Working Group 2014, CD8 expression assessed semiquantitatively after immunohistochemistry staining. Response to anthracycline-based neoadjuvant chemotherapy evaluated clinically using Response Evaluation Criteria in Solid Tumours (RECIST) criteria and pathologically by evaluating hematoxylin and eosin (H&E)-stained slides from mastectomy specimens after 3 or 4 cycles of neoadjuvant chemotherapy. RESULTS: Chi-squared analysis showed a significant relationship between TILs level and CD8 expression with chemotherapy responses clinically (p = 0.011 and p = 0.017 respectively) but not pathologically. Furthermore, the logistic regression test exhibit the predictive value of TILs level was 66.7% and CD8 expression was 64%. CONCLUSIONS: This study results suggest that TILs level and CD8 expression may be added as predictive factors to the response of anthracycline-based neoadjuvant chemotherapy, and oncologists may take benefit in breast cancer patient’s management.

Gene expression analysis of invasive breast carcinoma yields differential patterns in luminal subtypes of breast cancer

2021 ◽  
pp. 151814
Author(s):  
Ahmed S. Abdelhafiz ◽  
Merhan A. Fouda ◽  
Nahla A. Elzefzafy ◽  
Iman I. Taha ◽  
Omar M. Mohemmed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Breast Carcinoma ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Invasive Breast Carcinoma

Correlation of manual semi-quantitative and automated quantitative Ki-67 proliferative index with OncotypeDXTM recurrence score in invasive breast carcinoma

2021 ◽  
pp. 1-11
Author(s):  
Brian S. Finkelman ◽  
Amanda Meindl ◽  
Carissa LaBoy ◽  
Brannan Griffin ◽  
Suguna Narayan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Hot Spot ◽  
Recurrence Score ◽  
Invasive Breast Carcinoma ◽  
Chemotherapy Response ◽  
Scoring Method ◽  
Cancer Proliferation ◽  
Ki 67 ◽  
Breast Cancer Chemotherapy

BACKGROUND: Ki-67 immunohistochemistry (IHC) staining is a widely used cancer proliferation assay; however, its limitations could be improved with automated scoring. The OncotypeDXTM Recurrence Score (ORS), which primarily evaluates cancer proliferation genes, is a prognostic indicator for breast cancer chemotherapy response; however, it is more expensive and slower than Ki-67. OBJECTIVE: To compare manual Ki-67 (mKi-67) with automated Ki-67 (aKi-67) algorithm results based on manually selected Ki-67 “hot spots” in breast cancer, and correlate both with ORS. METHODS: 105 invasive breast carcinoma cases from 100 patients at our institution (2011–2013) with available ORS were evaluated. Concordance was assessed via Cohen’s Kappa (κ). RESULTS: 57/105 cases showed agreement between mKi-67 and aKi-67 (κ 0.31, 95% CI 0.18–0.45), with 41 cases overestimated by aKi-67. Concordance was higher when estimated on the same image (κ 0.53, 95% CI 0.37–0.69). Concordance between mKi-67 score and ORS was fair (κ 0.27, 95% CI 0.11–0.42), and concordance between aKi-67 and ORS was poor (κ 0.10, 95% CI −0.03–0.23). CONCLUSIONS: These results highlight the limits of Ki-67 algorithms that use manual “hot spot” selection. Due to suboptimal concordance, Ki-67 is likely most useful as a complement to, rather than a surrogate for ORS, regardless of scoring method.

Effects of Simvastatin on Breast Carcinoma Cell Proliferation and Apoptosis via Transforming Growth Factor-β1/Smad3 Pathway

2021 ◽  
Vol 11 (9) ◽  
pp. 1673-1682
Author(s):  
Feng Wang ◽  
Gengbao Qu ◽  
Baokai Wang
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Breast Carcinoma ◽  
Protein Expression ◽  
Breast Cancer Cell ◽  
Cell Apoptosis ◽  
Carcinoma Cell ◽  
Proliferation And Apoptosis ◽  
Smad3 Protein ◽  
Mcf 7

Objective: To investigate the function and causative role of simvastatin (Sim) in breast carcinoma cell apoptosis as well as proliferation. Methods: 20 breast carcinoma patients requiring surgery were treated with Sim (20 days, 30 mg), and samples of pre-treatment (pre) and post-treatment (post) were acquired. We detected tissue cell proliferation and apoptosis changes and used functional experiments to detect cell proliferation and apoptosis changes after treating not only estrogen receptor (ER)-positive (MCF-7) but also ER-negative cells (MDA-MB-231) with Sim or TGF-β1. Detection of p-Smad3 and total Smad3 protein expression changes was conducted, and we finally used in vivo experiments to assess the influence of Sim on breast tumor growth and drug safety. Results: Immunohistochemistry and TUNEL staining results showed that after treatment with Sim, breast carcinoma cell proliferation decreased and apoptosis increased. Functional experiments results showed that Sim notedly promoted the MDA-MB-231 and MCF-7 cell apoptosis, inhibiting migration, proliferation and epithelial mesenchymal transition. Moreover, TGF-β1 protein expression was strikingly lower in Sim group than that in DMSO group. When TGF-β1 and Sim were combined to use, the inhibitory ability of Sim on breast cancer cell proliferation markedly increased and the capability of TGF-β1 protein inducing p-Smad3 protein increased. In addition, after Sim treatment in mice, the tumor volume became smaller, the pathological changes weakened, and there was no significant effect on liver function and kidney function. Conclusion: Sim participates in breast cancer cell apoptosis and proliferation via regulating TGF-β1/Smad3 signal pathway.

Clinicopathological significance of WT1 expression in invasive breast carcinoma with >90% mucinous component

2021 ◽  
pp. jclinpath-2021-207464
Author(s):  
Xiaoli Xu ◽  
Rui Bi ◽  
Ruohong Shui ◽  
Baohua Yu ◽  
Yufan Cheng ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Growth Pattern ◽  
Histological Grade ◽  
Invasive Breast Carcinoma ◽  
Nuclear Grade ◽  
Proliferation Index ◽  
Her2 Overexpression ◽  
Ki 67 ◽  
Mucinous Component ◽  
Clinicopathological Significance

AimsThis study was aimed to investigate the clinicopathological significance of immunohistochemical (IHC) Wilm’s tumour 1 (WT1) expression in invasive breast carcinoma with >90% mucinous components.MethodsOne hundred specimens of invasive breast carcinoma with >90% mucinous component were collected. All H&E-stained slides were reviewed, and the clinicopathological data, including sex, age, tumour size, nuclear grade, histological grade, growth pattern and lymph node (LN) status, were collected. IHC staining of WT1, oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 was performed. Fluorescence in situ hybridisation was used to verify the amplification of the HER2 gene. The relationship between WT1 expression and clinicopathological features was analysed statistically.ResultsWT1 expression was detected in 67% (67/100) of invasive breast carcinoma with >90% mucinous components. WT1 expression was significantly associated with low-to-intermediate nuclear grade/histological grade, ER and PR positivity, HER2 negativity, Ki-67 proliferation index <30% and noLN metastasis (all p<0.001). Micropapillary architecture was observed in 80% of cases. WT1 expression was not significantly correlated with different percentage of micropapillary components (p=0.422). None of the histological grade 3 tumours, tumours with HER2 overexpression/amplification and triple-negative specimens showed WT1 expression.ConclusionsWT1 expression was significantly related with low-intermediate nuclear/histological grade, ER positivity, HER2 negativity, a lower Ki-67 proliferation index and no LN metastasis in invasive breast carcinoma with >90% mucinous component. The micropapillary growth pattern in this type of tumour did not show a specific relationship with WT1 expression.

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