Expression of E26 transformation specific-1 (ETS-1) in tumour-infiltrating lymphocytes (TILs) is adverse prognostic factor in invasive breast cancer

2021 ◽  
pp. 1-7
Author(s):  
Velibor Puzovic ◽  
Jasminka Jakic-Razumovic
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Invasive Breast Cancer ◽  
Histological Grade ◽  
Tumour Size ◽  
Disease Free Survival ◽  
Proliferation Index ◽  
Adverse Prognostic Factor ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

AIM OF THE STUDY: The microenvironment depicts the relationship between tumour cells and immune response, and every insight into stromal lymphocytes could contribute to explain their role and activity. E26 transformation specific-1 (ETS-1) is a transcription factor that is active in cell proliferation. We analysed its immunohistochemical expression in tumour infiltrating lymphocytes (TILs) in invasive breast cancer and correlated its immunohistochemical score (IHS) to traditional predictive and prognostic factors and survival. MATERIALS AND METHODS: The sample contains data of 121 patients with invasive breast cancer, not otherwise specified (NOS) who underwent mammectomy and lymphadenectomy in 2002 at the Clinical Hospital Centre Zagreb, Croatia. Paraffin blocks of the tumour tissue were collected from the pathological archive. Three representative areas of every patient were chosen and multiple tissue samples were made. Immunohistochemical staining with rabbit anti-ETS-1 (Novocastra, UK) and the ABC method was performed on a DAKO Autostainer. The expression of ETS-1 in stromal TILs was analysed on an Olympus 41 microscope. The IHS score was calculated and correlated with clinical and pathological parameters, as well as disease-free survival (DFS) and overall survival (OS). RESULTS: In almost all patients (95%), some expression of ETS-1 in TILs was found. A moderate/high score of ETS-1 correlated with larger tumour size and higher histological grade, high proliferation index and low progesterone receptors (PgR). The patients with moderate/high ETS-1 expression in TILs had shorter DFS than patients with weak/negative ETS-1 expression. CONCLUSION: In invasive breast cancer NOS, expression of ETS-1 in TILs is an adverse prognostic factor.

scholarly journals Immunohistochemical Evaluation of FGD3 Expression: A New Strong Prognostic Factor in Invasive Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3824
Author(s):  
Tommaso Susini ◽  
Giulia Saccardin ◽  
Irene Renda ◽  
Milo Giani ◽  
Enrico Tartarotti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Invasive Breast Cancer ◽  
Molecular Subtype ◽  
Histological Grade ◽  
Disease Free Survival ◽  
Individual Risk ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Cox Analysis

Among new prognostic factors for breast cancer, the most promising one seems to be FGD3 (Facio-Genital Dysplasia 3) gene, whose expression improves outcome by inhibiting cell migration. The aim of the study was to evaluate the prognostic role of FGD3 in invasive breast cancer in a series of 401 women, treated at our unit, by evaluating the expression of this gene by immunohistochemistry. Patients with high FGD3 expression showed a significantly better disease-free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001). The prognostic value of FGD3 expression was stronger than that of classical pathologic parameters such as histological grade of differentiation, Ki-67 index and molecular subtype. By multivariate Cox analysis, FGD3 expression was confirmed as significant and independent prognostic factor, ranking second after age at diagnosis (≤40 years) for DFS (p = 0.003) and the second strongest predictor of OS, after AJCC Stage (p < 0.001). Our data suggest that inclusion of FGD3 evaluation in the routine workup of breast cancer patients may result in a more accurate stratification of the individual risk. The possibility to assess FGD3 expression by a simple and cheap technique such as immunohistochemistry may enhance the spread of its use in the clinical practice.

A retrospective study of immunohistochemical detection of Ki67 and correlation with ER, PR, and HER2-neu status in invasive breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21132-e21132
Author(s):  
Deepa Meda Prakash ◽  
Swarna Shivakumar ◽  
P P Bapsy
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Tumor Size ◽  
Histological Grade ◽  
Biological Behavior ◽  
Proliferation Index ◽  
Poor Correlation ◽  
Nuclear Staining ◽  
Ki 67 ◽  
Therapeutic Decisions

e21132 Background: Carcinoma breast is a heterogeneous group of disease. Several prognostic factors are known to predict the biological behavior and clinical outcome of breast cancer, including proliferation index, tumor size, age, histological grade, hormone receptors and Her2Neu status. Of theses proliferative index is the most important parameter in predicting tumor aggressiveness and prognosis. Ki67 is a nuclear protein, tightly linked to the cell cycle and is a marker of cell proliferation. High Ki67 usually correlates with a poor prognosis in breast cancer. Methods: This exploratory study is initiated whether Ki67 will be an additional prognostic factor. Immunohistochemical staining of Ki 67 was performed on formalin fixed paraffin embedded blocks of 50 cases of histologically confirmed breast cancer. Ki 67 expression based on distinct nuclear staining of tumor cells was assessed semiquantitatively as, nil (no immunostaining), low (≤10% immunopositivity), high (>10% immunopositivity) by light microscope. ER, PR, Her 2neu status and clinico-pathological parameters were analyzed and correlated with Ki67 immunostaining using the x2 test. Results: Our study showed high Ki 67 staining in 24 cases(48%), low immunostaining in 18 cases(36%) and was nil in 5 cases (10%) and was inconclusive in 3 cases(6%) (core biopsies). There was an inverse correlation of Ki 67 with ER, PR scores in 32 cases (64%) and positive correlation was seen in 28 cases (56%) with Her2 neu status. A good correlation was also observed with mitotic index in 37cases (74%) and histological grade in 29 cases (58%). Good correlation was seen with large tumor size in 24 cases(48%) and metastatic disease 9 cases (64%). Poor correlation was observed with node positive 22 cases (44%). High Ki 67 expression with good treatment response was seen in 13 cases (26%). Conclusions: Based on our study, Ki 67 score may prove to be an important prognostic factor in breast cancer and thereby, useful in making therapeutic decisions. But this is being explored in a large prospective study.

Clinicopathologic Parameters and Survival Data in Non-Metastatic Breast Cancer Patients in Correlation with Tumour Infiltrating Lymphocytes, Androgen Receptor and Insulin-Like Growth Factor Receptor 1 Expression

2020 ◽  
Vol 106 (1_suppl) ◽  
pp. 26-26
Author(s):  
JM Njenga ◽  
A El-Gowily ◽  
WO Arafat ◽  
D Abdalla ◽  
YA Rostom
Keyword(s):  
Breast Cancer ◽  
Carcinoma In Situ ◽  
Prognostic Value ◽  
Tumour Size ◽  
Disease Free Survival ◽  
Free Survival ◽  
Clinicopathologic Parameters ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Introduction: The constantly evolving nature of breast cancer (BC) makes it paramount to identify and evaluate more biomarkers that may have a predictive and prognostic value. We explored the relationship between the androgen receptor (AR), insulin-like growth factor 1 receptor (IGF-1R) and tumour infiltrating lymphocytes (TILs), and clinicopathologic variables and survival in BC. Materials and Methods: In this retrospective study, we collected clinical and pathological data of 105 BC patients who had been treated at Alexandria Main University Hospitals from January 2010 to December 2016. These patients’ formalin fixed paraffin-embedded blocks were retrieved and analyzed for AR and IGF-1R expression immunohistochemically; TILs were assessed by hematoxylin and eosin staining. Chi square and Kaplan Meier curves were used to study the correlation between the three biomarkers and clinicopathologic parameters and survival respectively. Results: 59% and 51.4% of patients were AR and IGF-1R positive respectively. AR immunoreactivity correlated with a tumour size less than 5 centimeters (p=0.001), presence of carcinoma in situ (p=0.008), negative Her 2 status (p=0.007) and negative lymphovascular invasion (p<0.001). Negative AR expression predicted a longer disease free survival (p=0.017). A positive IGF-1R was associated with carcinoma in situ (p<0.001) and negative extra-nodal extension (p=0.042) but no impact on the disease free survival (p=0.227). A high TIL expression was associated with a tumour size less than 5 centimeters (p=0.005), invasive lobular carcinoma (p=0.006), carcinoma in situ (p=0.047), negative LVI (p<0.001) and longer survival. A positive AR expression was associated with a positive IGF-1R expression (p<0.001). Conclusions: AR, IGF-1R and TILs correlate differently with various clinicopathologic variables used in BC; in addition they all have a prognostic value. The two receptors are a promising target in BC. More clinical studies are required to further confirm the utility of these three biomarkers.

scholarly journals The tumor-infiltrating effector regulatory T cell:CD8+ lymphocyte ratio in invasive breast cancer

2019 ◽  
Author(s):  
Morihito Okada ◽  
Noriko Goda ◽  
Shinsuke Sasada ◽  
Hideo Shigematsu ◽  
Norio Masumoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Invasive Breast Cancer ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Compete Response ◽  
Infiltrating Lymphocytes

Abstract Background Tumor-infiltrating lymphocytes (TILs) in breast cancer comprise immunostimulating and immunosuppressive components. Although FOXP3+ TILs are prototypical immunosuppressive TILs, only effector regulatory T cells (eTreg), a subset of immunosuppressive FOXP3+ TILs, are undetectable on immunohistochemical staining. This study aimed to evaluate the immunosuppressive potential of eTregs and the role of prototypical immunostimulatory CD8+ TILs in invasive breast cancer. Methods Fresh TILs extracted from 84 invasive breast cancer patients were analyzed via flow cytometry. We evaluated eTregs (CD4+FOXP3highCD45RA−), other FOXP3+ Treg subsets (naïve and non-Tregs), and total CD8+CD4- TILs. Clinicopathological factors, including histopathological characteristics, were also assessed. Results The median eTreg proportion of the total CD4+TILs was 18.7% (interquartile range [IQR], 16.4–25.5%); CD8+TILs, 124% (IQR, 87.5–140%). The proportion of eTregs to total FOXP3+ TILs varied (median, 65.6%; range, 10.1–93.2%). In an immunosuppression assay, only eTregs displayed potent immunosuppression; however, other Treg subsets did not. Among 39 patients who received neoadjuvant chemotherapy, eTreg subsets and pathological compete response (pCR) did not differ significantly, while pCR rates were significantly higher among individuals with a high than those with a low CD8+/eTreg ratio (90.2% vs 33.3%; P<0.05). Among all patients, a high CD8+/eTreg ratio tended to be associated with better disease-free survival rather than a low CD8+/eTreg ratio (P=0.09). Conclusions The CD8+/eTreg ratio is simple, optimal indicator of cancer immunity, and a high CD8+/eTreg ratio enhances the prognosis and treatment response in invasive breast cancer patients. However, further studies are required to validate the present findings.

scholarly journals Correlation between Ki-67 proliferation index in invasive breast cancer and molecular signatures: EndoPredict and MammaPrint

2021 ◽  
Author(s):  
J. Eduardo Amezcua-Gálvez ◽  
Carlos A. Lopez-Garcia ◽  
Villarreal-Garza Cynthia ◽  
Lopez-Rivera Victor ◽  
Canavati-Marcos Mauricio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Risk Stratification ◽  
Invasive Breast Cancer ◽  
Histological Grade ◽  
Area Under The Curve ◽  
Molecular Signature ◽  
Proliferation Index ◽  
Molecular Signatures ◽  
Ki 67

Abstract Background: The need to identify patients with hormone receptor-positive (HR+) early invasive breast cancer (EIBC) who could benefit from adjuvant chemotherapy has been enhanced with the development of molecular signature tests. However, due to their high cost and limited availability alternative low-cost prognostic and predictive tests are used in clinical practice. Here, we sought to evaluate the performance of the proliferation marker Ki-67 to identify these patients and explore its association with molecular signatures and risk stratification markers. Methods: From our prospectively maintained multicenter breast cancer registry, we identified EIBC HR+ patients tested with EndoPredict or MammaPrint and Ki-67 as part of their routine workup. Patients were categorized into two groups: Group 1 (2016-2018) was evaluated using EndoPredict and Group 2 (2011 to 2018) with MammaPrint. A ≥20% Ki67 cutoff was utilized for identify high proliferative EIBC and a receiver-operative curve area under the curve (AUC) and kappa concordance were utilized to evaluate the performance of Ki-67 compared to molecular signature tests. Results: In the EndoPredict group, 54/96 patients were considered high-risk by EPclin. 57/96 patients had a Ki-67 ≥20%. However, there was no significant overall concordance between them (59.37%, κ = 0.168, p=0.09). In the MammaPrint group, 21/70 patients were considered high-risk. Ki67 ≥20% was present in 36 patients with a significant overall concordance (67.14%, κ 0.35, p<0.001). Additionally, Ki-67 was associated with the Nottingham histological grade (NHG) in both groups. Conclusion: There is a fair concordance between Ki-67 and MammaPrint risk stratification of HR + EIBC and no concordance with EndoPredict molecular signature. Cost-effectiveness analysis of these tests in developing countries are needed, until then, the use of Ki-67 seems reasonable to aid clinical decision.

scholarly journals Tumour-infiltrating lymphocytes in non-invasive breast cancer: A systematic review and meta-analysis

The Breast ◽  
2021 ◽  
Author(s):  
Rafael Caparica ◽  
Marco Bruzzone ◽  
Elisa Agostinetto ◽  
Maria Alice Franzoi ◽  
Marcello Ceppi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Invasive Breast Cancer ◽  
Meta Analysis ◽  
Non Invasive ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

Co-expression of ER-beta and HER2 associated with poorer prognosis in primary breast cancer

2009 ◽  
Vol 32 (3) ◽  
pp. 250 ◽  
Author(s):  
Wen-sheng Qui ◽  
Lu Yue ◽  
Ai-ping Ding ◽  
Jian Sun ◽  
Yang Yao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Differentiation ◽  
Primary Breast Cancer ◽  
Tumour Size ◽  
Univariate Analysis ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Er Alpha

Purpose: To assess the prognostic value of co-expression of estrogen receptor (ER)-beta and human epidermal growth factor receptor 2 (HER2) in primary breast cancer patients in China. Methods: Tumour specimens from 308 patients undergoing surgery for primary breast cancer were evaluated. Expression of ER-beta and HER-2 was investigated by the immunohistochemistry. Results: 123 patients (40%) were ER-beta positive and 58 (18.5 %) were HER2 positive. Among the 58 HER2 positive patients, 44 were ER-beta positive and 14 were ER-beta negative. ER-beta positive was associated with HER2 positive (75.9%, P=0.018) as well as ER-alpha positive (79.7%, P=0.023), poor cell differentiation (77.2% grade 2 or 3, P=0.010) and menopause age < 45 yr (55.3%, P=0.031). HER2 positive was associated with poor cell differentiation (93.1%, P=0.001), ?3cm tumour size (67.2%, P=0.011). Conclusion: Both ER-beta positive and HER2 positive status was associated with poorer overall survival (OS) by univariate analysis. In both HER2 positive and HER2 negative subgroups, ER-beta positive was associated with poorer distant disease free survival (DDFS) but not OS, which implied that ER-beta might relate to metastasis in breast cancer.

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.

scholarly journals Cancer Grade Model: a multi-gene machine learning-based risk classification for improving prognosis in breast cancer

2021 ◽  
Author(s):  
E. Amiri Souri ◽  
A. Chenoweth ◽  
A. Cheung ◽  
S. N. Karagiannis ◽  
S. Tsoka
Keyword(s):  
Breast Cancer ◽  
Machine Learning ◽  
Clinical Decision Making ◽  
Histological Grade ◽  
Tumour Size ◽  
Clinical Decision ◽  
Gene Signature ◽  
Risk Classification ◽  
Breast Cancers ◽  
Grade 3

Abstract Background Prognostic stratification of breast cancers remains a challenge to improve clinical decision making. We employ machine learning on breast cancer transcriptomics from multiple studies to link the expression of specific genes to histological grade and classify tumours into a more or less aggressive prognostic type. Materials and methods Microarray data of 5031 untreated breast tumours spanning 33 published datasets and corresponding clinical data were integrated. A machine learning model based on gradient boosted trees was trained on histological grade-1 and grade-3 samples. The resulting predictive model (Cancer Grade Model, CGM) was applied on samples of grade-2 and unknown-grade (3029) for prognostic risk classification. Results A 70-gene signature for assessing clinical risk was identified and was shown to be 90% accurate when tested on known histological-grade samples. The predictive framework was validated through survival analysis and showed robust prognostic performance. CGM was cross-referenced with existing genomic tests and demonstrated the competitive predictive power of tumour risk. Conclusions CGM is able to classify tumours into better-defined prognostic categories without employing information on tumour size, stage, or subgroups. The model offers means to improve prognosis and support the clinical decision and precision treatments, thereby potentially contributing to preventing underdiagnosis of high-risk tumours and minimising over-treatment of low-risk disease.

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