scholarly journals TGFB-Induced Factor Homeobox 1 (TGIF) Expression in Breast Cancer

2021 ◽  
Author(s):  
Christine Stürken ◽  
Volker Möbus ◽  
Karin Milde-Langosch ◽  
Sabine Schmatloch ◽  
Peter Fasching ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Univariate Analysis ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Er Positive ◽  
Registration Number ◽  
Strong Staining ◽  
Well Differentiated ◽  
Dose Dense ◽  
Formalin Fixed

Abstract Background: Breast cancer (BC) is the most frequent female cancer its which preferentially metastasizes to bone. Mechanisms of bone tropism are poorly understood, however, the transcription factor TGFB-induced factor homeobox 1 (TGIF) is involved in bone metabolism and thus of potential interest.Methods: TGIF expression was analyzed by immunohistochemistry in 1197 formalin-fixed, paraffin-embedded tissue from BC patients treated in the GAIN study with two adjuvant dose-dense schedules of chemotherapy with or without bisphosphonate ibandronate. TGIF expression was categorized into negative/low and moderate/strong staining.Results: In 1197 samples, we found associations of higher TGIF protein expression with smaller tumor size (p = 0.015), well differentiated phenotype (p < 0.001) and estrogen receptor (ER)-positive BC (p < 0.001). Patients with higher TGIF expression levels showed a significantly better disease-free (log-rank p 0.019) and overall survival (log-rank p = 0.018), but no association with time to bone metastasis as first site of relapse. Stratified univariate analysis in molecular subgroups emphasized that elevated TGIF expression was prognostic for both DFS and OS in ER-positive BC patients (DFS: log-rank p = 0.009; OS: log-rank p = 0.008) and in the HER2-negative subgroup (DFS: log-rank p = 0.004; OS: log-rank p = 0.002).Conclusions: Our findings suggest that a loss of TGIF expression is associated with BC progression, especially in luminal carcinomas.Trial registration: This clinical trial has been registered with ClinicalTrials.gov; registration number: NCT00196872.

scholarly journals Comparison of the RNA-based EndoPredict multigene test between core biopsies and corresponding surgical breast cancer sections

2012 ◽  
Vol 65 (7) ◽  
pp. 660-662 ◽  
Author(s):  
Berit Maria Müller ◽  
Jan C Brase ◽  
Franziska Haufe ◽  
Karsten E Weber ◽  
Jan Budzies ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Paired Samples ◽  
Biopsy Tissue ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Er Positive ◽  
Highly Correlated ◽  
Inflammatory Changes ◽  
Test Result ◽  
Formalin Fixed

AimThis study compared the perfomance of the RNA-based EndoPredict multigene test on core biopsies and surgical breast cancer specimens and analysed the influence of biopsy-induced tissue injuries on the test result.Methods80 formalin-fixed paraffin-embedded samples comprising paired biopsies and surgical specimens from 40 ER-positive, HER2-negative patients were evaluated. Total RNA was extracted and the EndoPredict score was determined.ResultsRNA yield was considerably lower in core biopsies, but sufficient to measure the assay in all samples. The EndoPredict score was highly correlated between paired samples (Pearson r=0.92), with an excellent concordance of classification into a low or high risk of metastasis (overall agreement 95%).ConclusionsThe measurements are comparable between core biopsies and surgical sections, which suggest that the EndoPredict assay can be performed on core biopsy tissue. Inflammatory changes induced by presurgical biopsies had no significant effect on the RNA-based risk assessment in surgical specimens.

scholarly journals Overexpression of circulating MiR-30b-5p identifies advanced breast cancer

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Helena Estevão-Pereira ◽  
João Lobo ◽  
Sofia Salta ◽  
Maria Amorim ◽  
Paula Lopes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Validation Cohort ◽  
Advanced Disease ◽  
Clinical Tool ◽  
Liquid Biopsies ◽  
Primary Tumors ◽  
Bodily Fluids ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

Abstract Background Breast cancer (BrC) remains the leading cause of cancer-related death in women, mainly due to recurrent and/or metastatic events, entailing the need for biomarkers predictive of progression to advanced disease. MicroRNAs hold promise as noninvasive cancer biomarkers due to their inherent stability and resilience in tissues and bodily fluids. There is increasing evidence that specific microRNAs play a functional role at different steps of the metastatic cascade, behaving as signaling mediators to enable the colonization of a specific organ. Herein, we aimed to evaluate the biomarker performance of microRNAs previously reported as associated with prognosis for predicting BrC progression in liquid biopsies. Methods Selected microRNAs were assessed using a quantitative reverse transcription-polymerase chain reaction in a testing cohort of formalin-fixed paraffin-embedded primary (n = 16) and metastatic BrC tissues (n = 22). Then, miR-30b-5p and miR-200b-3p were assessed in a validation cohort #1 of formalin-fixed paraffin-embedded primary (n = 82) and metastatic BrC tissues (n = 93), whereas only miR-30b-5p was validated on a validation cohort #2 of liquid biopsies from BrC patients with localized (n = 20) and advanced (n = 25) disease. ROC curve was constructed to evaluate prognostic performance. Results MiR-30b-5p was differentially expressed in primary tumors and paired metastatic lesions, with bone metastases displaying significantly higher miR-30b-5p expression levels, paralleling the corresponding primary tumors. Interestingly, patients with advanced disease disclosed increased circulating miR-30b-5p expression compared to patients with localized BrC. Conclusions MiR-30b-5p might identify BrC patients at higher risk of disease progression, thus, providing a useful clinical tool for patients’ monitoring, entailing earlier and more effective treatment. Nonetheless, validation in larger multicentric cohorts is mandatory to confirm these findings.

scholarly journals The impact of RNA extraction method on accurate RNA sequencing from formalin-fixed paraffin-embedded tissues

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Michal Marczyk ◽  
Chunxiao Fu ◽  
Rosanna Lau ◽  
Lili Du ◽  
Alexander J. Trevarton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Rna Sequencing ◽  
Rna Extraction ◽  
Formalin Fixed Paraffin ◽  
Ffpe Samples ◽  
Formalin Fixed Paraffin Embedded ◽  
The Impact ◽  
Formalin Fixed

Abstract Background Utilization of RNA sequencing methods to measure gene expression from archival formalin-fixed paraffin-embedded (FFPE) tumor samples in translational research and clinical trials requires reliable interpretation of the impact of pre-analytical variables on the data obtained, particularly the methods used to preserve samples and to purify RNA. Methods Matched tissue samples from 12 breast cancers were fresh frozen (FF) and preserved in RNAlater or fixed in formalin and processed as FFPE tissue. Total RNA was extracted and purified from FF samples using the Qiagen RNeasy kit, and in duplicate from FFPE tissue sections using three different kits (Norgen, Qiagen and Roche). All RNA samples underwent whole transcriptome RNA sequencing (wtRNAseq) and targeted RNA sequencing for 31 transcripts included in a signature of sensitivity to endocrine therapy. We assessed the effect of RNA extraction kit on the reliability of gene expression levels using linear mixed-effects model analysis, concordance correlation coefficient (CCC) and differential analysis. All protein-coding genes in the wtRNAseq and three gene expression signatures for breast cancer were assessed for concordance. Results Despite variable quality of the RNA extracted from FFPE samples by different kits, all had similar concordance of overall gene expression from wtRNAseq between matched FF and FFPE samples (median CCC 0.63–0.66) and between technical replicates (median expression difference 0.13–0.22). More than half of genes were differentially expressed between FF and FFPE, but with low fold change (median |LFC| 0.31–0.34). Two out of three breast cancer signatures studied were highly robust in all samples using any kit, whereas the third signature was similarly discordant irrespective of the kit used. The targeted RNAseq assay was concordant between FFPE and FF samples using any of the kits (CCC 0.91–0.96). Conclusions The selection of kit to purify RNA from FFPE did not influence the overall quality of results from wtRNAseq, thus variable reproducibility of gene signatures probably relates to the reliability of individual gene selected and possibly to the algorithm. Targeted RNAseq showed promising performance for clinical deployment of quantitative assays in breast cancer from FFPE samples, although numerical scores were not identical to those from wtRNAseq and would require calibration.

Osteopontin Expression According to Molecular Profile of Invasive Breast Cancer: A Clinicopathological and Immunohistochemical Study

2008 ◽  
Vol 23 (3) ◽  
pp. 154-160 ◽  
Author(s):  
A. Ribeiro-Silva ◽  
J.P. Oliveira da Costa ◽  
S. Britto Garcia
Keyword(s):  
Breast Cancer ◽  
Calcium Binding ◽  
Molecular Profile ◽  
Breast Carcinomas ◽  
Formalin Fixed Paraffin ◽  
Mineralized Tissues ◽  
Formalin Fixed Paraffin Embedded ◽  
Invasive Breast Carcinomas ◽  
Formalin Fixed

Osteopontin (OPN) is a secreted, calcium-binding phosphorylated glycoprotein involved in several physiological and pathological events such as angiogenesis, apoptosis, inflammation, wound healing, vascular remodeling, calcification of mineralized tissues, and induction of cell proteases. There is growing interest in the role of OPN in breast cancer. In an attempt to obtain new insight into the pathogenesis of OPN-associated breast carcinomas, an immunohistochemical panel with 17 primary antibodies including cytokeratins and key regulators of the cell cycle was performed in 100 formalin-fixed paraffin-embedded samples of invasive breast carcinomas. OPN was expressed in 65% of tumors and was negatively correlated with estrogen (p=0.0350) and progesterone (p=0.0069) receptors, but not with the other markers and clinicopathological features evaluated including age, menstrual status, pathological grading, tumor size, and metastasis. There was no correlation between OPN expression and carcinomas of the basal-like phenotype (p=0.1615); however, OPN correlated positively with c-erbB-2 status (p=0.0286) and negatively with carcinomas of the luminal subtype (p=0.0353). It is well known that carcinomas overexpressing c-erbB-2 protein have a worse prognosis than luminal tumors. Here, we hypothesize that the differential expression of OPN in the first subtype of carcinomas may contribute to their more aggressive behavior.

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