scholarly journals Expression of VEGF in breast lesions: an immunohistochemical study

2019 ◽  
Vol 6 (1) ◽  
pp. 12
Author(s):  
Shuaeb Bhat ◽  
Tania R. P. ◽  
Saleem Hussain ◽  
Bushra Sahaf ◽  
Irfan Ansari
Keyword(s):  
Breast Cancer ◽  
Breast Tissue ◽  
Normal Breast Tissue ◽  
Genetic Alterations ◽  
Normal Breast ◽  
P Value ◽  
Breast Lesions ◽  
Chi Square ◽  
Malignant Breast ◽  
Benign Breast Lesions

Background: Breast cancer is the most frequent cancer in India. During the last few years, several investigators have focused on tumor angiogenesis as a critical step in cancer development and progression. Among these, vascular endothelial growth factor (VEGF) is emerging as a prognostic marker in patients with several type of cancer including breast cancer. The aim of the study was to analyse the expression of VEGF in human breast cancer as compared to normal breast tissue and benign breast lesions by immunohistochemistry. Also, to assess the usefulness of VEGF as a predictor of aggressiveness of breast lesions.Methods: Formalin fixed paraffin embedded sections of 10 cases of normal breast tissue, 20 cases of benign breast lesions and 20 cases of malignant breast lesions were taken up for the study and subjected to immunohistochemistry using VEGF.Results: The intensity of VEGF immunostaining in normal breast, benign and malignant breast lesions was evaluated and scoring was graded as 0, 1+, 2+, 3+ and 4+. Statistical analysis was performed with Chi-Square test and significant differences were noted between these 3 groups (p value <0.05).Conclusions:VEGF expression correlated well with the grade and stage of tumor indicating that VEGF positive tumors are biologically aggressive and are associated with poor prognosis but little is known about the implication of genetic alterations of VEGF in benign breast lesions.

scholarly journals Association between cadmium and breast cancer

Medicina ◽  
2008 ◽  
Vol 44 (6) ◽  
pp. 415 ◽  
Author(s):  
Loreta Strumylaitė ◽  
Algirdas Boguševičius ◽  
Stanislovas Ryselis ◽  
Darius Pranys ◽  
Lina Poškienė ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Tissue ◽  
Benign Tumor ◽  
Normal Breast Tissue ◽  
Cadmium Concentration ◽  
Normal Breast ◽  
Tissue Samples ◽  
Malignant Breast Tissue ◽  
Two Samples ◽  
Malignant Breast

Cadmium is a known human lung carcinogen, although some studies indicate a link between cadmium exposure and human breast cancer. The objective of this study was to assess cadmium concentration in breast tissue samples of patients with breast cancer and benign breast tumor. Material and methods. The concentration of cadmium was determined in breast tissue samples of 21 breast cancer and 19 benign tumor patients. Two samples of breast tissue from each patient, i.e. tumor and normal tissue close to tumor, were taken for the analysis. Cadmium was determined by atomic absorption spectrometry (Perkin-Elmer, Zeeman 3030). Results. In patients with breast cancer, the mean cadmium concentration was 33.1 ng/g (95% CI, 21.9– 44.4) in malignant breast tissue and 10.4 ng/g (95% CI, 5.6–15.2) in normal breast tissue (P=0.002). In patients with benign tumor, the corresponding values were 17.5 ng/g (95% CI, 8.4–26.5) and 11.8 ng/g (95% CI, 5.1– 18.5) (P=0.3144). There was a statistically significant difference in cadmium concentration between malignant and benign breast tissues (P=0.009). Conclusion. The data obtained show that cadmium concentration is significantly higher in malignant breast tissue as compared with normal breast tissue of the same women or benign breast tissue. Further studies are necessary to determine the association between cadmium concentration in malignant breast tissue and estrogen receptor level, and smoking.

Expression of a cancer associated isoform of PCNA in breast cancer has implications as a potential biomarker

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21069-21069
Author(s):  
L. H. Malkas ◽  
L. A. Schnaper ◽  
B. Herbert ◽  
W. Abdel-Aziz ◽  
Y. Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Tissue ◽  
Normal Breast Tissue ◽  
Normal Breast ◽  
Definitive Diagnosis ◽  
Nuclear Antigen ◽  
Average Percentage ◽  
Potential Biomarker ◽  
Malignant Breast ◽  
Breast Cells

21069 Background: We have identified a novel cancer associated isoform of the protein, proliferating cell nuclear antigen (PCNA), termed (caPCNA), and demonstrated that this isoform arises through a direct protein post-translational modification, and not via genetic mutation or RNA splice variation. Our results suggest that caPCNA has the potential to serve as a highly effective and unique marker for identifying malignant breast cancer cells. Methods: This assertion is based on our proteomic-based analyses of more than 60 malignant and non- malignant breast cell lines and tissues. Commercially available antibodies against PCNA cannot distinguish between the different isoforms of PCNA present in malignant and non-malignant breast cells and cannot be used clinically to differentiate between normal and malignant breast tissue. However, we have recently developed a rabbit polyclonal antibody, (caPCNAab), which specifically recognizes only the caPCNA isoform expressed by malignant human breast cells. Results: Using this antibody we clearly show that caPCNA is expressed only in malignant breast cells and tissues, and can be found in early disease. caPCNA expression in tissues was quantified as average staining intensity X average percentage of cells stained. Using this criterion the following data were obtained: 10 cases of normal breast tissue (reduction mammoplasty) gave a total score of 1%; 35 cases of normal breast tissue adjacent to malignancy scored as 4%; 30 cases of DCIS scored as 90%; and 55 cases of invasive breast carcinoma scored as 120%. The five cases of ADH examined thus far were shown to score similar to that of normal breast tissue. Conclusions: The implication of these data is that the development of a caPCNAab-based IHC stain could potentially be used to reliably stain only in situ or invasive carcinoma, and distinguish genuinely benign lesions (e.g., ADH) from carcinoma, (e.g., DCIS) allowing definitive diagnosis in such cases where a limited amount of an atypical lesion prevents definitive diagnosis on routine H/E stained sections alone. For the patient population, this could result in a marked decrease in the need for either a repeat core biopsy or an excisional biopsy due to an inconclusive initial diagnosis. No significant financial relationships to disclose.

Plasma kinetics, uptake by neoplastic breast tissue and preliminary toxicity data of a cholesterol-rich microemulsion (LDE) associated to a paclitaxel (PCT) derivative

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12038-12038
Author(s):  
L. A. Pires ◽  
R. Hegg ◽  
S. R. Graziani ◽  
D. G. Rodrigues ◽  
R. C. Maranhão ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Tissue ◽  
Normal Breast Tissue ◽  
Normal Breast ◽  
Pharmacokinetic Parameters ◽  
Toxicity Data ◽  
Breast Cancer Patients ◽  
Plasma Kinetics ◽  
Malignant Breast Tissue ◽  
Malignant Breast

12038 Background: Previously we described the association of PCT to a cholesterol-rich microemulsion (LDE) that binds to low-density lipoprotein (LDL) receptors and concentrates in neoplastic tissues. The association is stable, preserves the anti-proliferative activity and reduces the toxicity to animals. The present study was designed to provide preliminary toxicity data on the LDE-PCT oleate formulation, to determine its plasma kinetics compared to that of commercial PCT and to verify the complex ability to concentrate in malignant breast tissue. Methods: To determine the plasma kinetics [3H]-PCT oleate associated to LDE labeled with [14C]-Cholesteryl oleate was intravenously injected into 3 pts and [3H]-commercial PCT into 2 pts 24 h before surgery. Blood samples were collected over the 24 h to quantified radioactivity and the pharmacokinetic parameters. Tumoral and normal breast tissue were excised during the surgery. Other 3 heavily pretreated pts with breast cancer were included in this study to assess toxicity. LDE-PCT (175 mg/m2) was administered as a 1-hour infusion at 3 week interval, without pre medication. Results: Fractional clearance rate (FCR) of LDE and of the drug were similar (0.030 ± 0.026 e 0.018 ± 0.018, respectively, P = 0.5742). The uptake of both [14C]-LDE and [3H]-paclitaxel oleate by breast malignant tissue was 2 and 3 fold greater than that of the normal breast tissue. The PCT oleate T1/2 (h) was greater than the commercial PCT (T½ = 18.97 ± 7.7 and 7.34 ± 0.40) and the clearence (L/h) of PCT oleate was lesser than the commercial (CL = 1.51 ± 0.18 and 7.95 ± 4.32). No hematological or neurotoxicity was found. Nausea and anorexia grade 1 was found only in one patient. Conclusion: Most of the drug is retained in the microemulsion until its removal from the circulation. The complex is stable and has greater plasma half life and lesser clearance than those for commercial one and can be concentrated in malignant breast tissue. Furthermore, LDE-PCT showed no considerable toxicity events in the 3 patients. Although data regarding response rates were not assessed, our preliminary results suggest that LDE-PCT may be a suitable and powerful weapon to treat breast cancer patients. No significant financial relationships to disclose.

scholarly journals Accelerated aging in normal breast tissue of women with breast cancer

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Shoghag Panjarian ◽  
Jozef Madzo ◽  
Kelsey Keith ◽  
Carolyn M. Slater ◽  
Carmen Sapienza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Anomaly Detection ◽  
Breast Tissue ◽  
Preventive Intervention ◽  
Normal Breast Tissue ◽  
Accelerated Aging ◽  
Normal Breast ◽  
Age Related ◽  
Unsupervised Anomaly Detection

Abstract Background DNA methylation alterations have similar patterns in normal aging tissue and in cancer. In this study, we investigated breast tissue-specific age-related DNA methylation alterations and used those methylation sites to identify individuals with outlier phenotypes. Outlier phenotype is identified by unsupervised anomaly detection algorithms and is defined by individuals who have normal tissue age-dependent DNA methylation levels that vary dramatically from the population mean. Methods We generated whole-genome DNA methylation profiles (GSE160233) on purified epithelial cells and used publicly available Infinium HumanMethylation 450K array datasets (TCGA, GSE88883, GSE69914, GSE101961, and GSE74214) for discovery and validation. Results We found that hypermethylation in normal breast tissue is the best predictor of hypermethylation in cancer. Using unsupervised anomaly detection approaches, we found that about 10% of the individuals (39/427) were outliers for DNA methylation from 6 DNA methylation datasets. We also found that there were significantly more outlier samples in normal-adjacent to cancer (24/139, 17.3%) than in normal samples (15/228, 5.2%). Additionally, we found significant differences between the predicted ages based on DNA methylation and the chronological ages among outliers and not-outliers. Additionally, we found that accelerated outliers (older predicted age) were more frequent in normal-adjacent to cancer (14/17, 82%) compared to normal samples from individuals without cancer (3/17, 18%). Furthermore, in matched samples, we found that the epigenome of the outliers in the pre-malignant tissue was as severely altered as in cancer. Conclusions A subset of patients with breast cancer has severely altered epigenomes which are characterized by accelerated aging in their normal-appearing tissue. In the future, these DNA methylation sites should be studied further such as in cell-free DNA to determine their potential use as biomarkers for early detection of malignant transformation and preventive intervention in breast cancer.

scholarly journals Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions

2020 ◽  
Author(s):  
Toshiaki Akahane ◽  
Naoki Kanomata ◽  
Oi Harada ◽  
Tetsumasa Yamashita ◽  
Junichi Kurebayashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Tumor ◽  
Primary Breast Cancer ◽  
Breast Tissue ◽  
Normal Breast Tissue ◽  
Metastatic Breast ◽  
Normal Breast ◽  
Human Breast ◽  
Metastatic Lesions ◽  
Generation Sequencing

Abstract Background: Next-generation sequencing (NGS) has shown that recurrent/metastatic breast cancer lesions may have additional genetic changes compared with the primary tumor. These additional changes may be related to tumor progression and/or drug resistance. However, breast cancer-targeted NGS is not still widely used in clinical practice to compare the genomic profiles of primary breast cancer and recurrent/metastatic lesions.Methods: Triplet samples of genomic DNA were extracted from each patient’s normal breast tissue, primary breast cancer, and recurrent/metastatic lesion(s). A DNA library was constructed using the QIAseq Human Breast Cancer Panel (93 genes, Qiagen) and then sequenced using MiSeq (Illumina). The Qiagen web portal was utilized for data analysis.Results: Successful results for three or four samples (normal breast tissue, primary tumor, and at least one metastatic/recurrent lesion) were obtained for 11 of 35 breast cancer patients with recurrence/metastases (36 samples). We detected shared somatic mutations in all but one patient, who had a germline mutation in TP53. Additional mutations that were detected in recurrent/metastatic lesions compared with primary tumor were in genes including TP53 (three patients) and one case each of ATR, BLM, CBFB, EP300, ERBB2, MUC16, PBRM1, and PIK3CA. Actionable mutations and/or copy number variations (CNVs) were detected in 73% (8/11) of recurrent/metastatic breast cancer lesions.Conclusions: The QIAseq Human Breast Cancer Panel assay showed that recurrent/metastatic breast cancers sometimes acquired additional mutations and CNV. Such additional genomic changes could provide therapeutic target.

scholarly journals DNA Methylation and Breast Cancer Risk: An Epigenome-Wide Study of Normal Breast Tissue and Blood

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3088 ◽  
Author(s):  
Kaoutar Ennour-Idrissi ◽  
Dzevka Dragic ◽  
Elissar Issa ◽  
Annick Michaud ◽  
Sue-Ling Chang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Breast Tissue ◽  
Normal Breast Tissue ◽  
Normal Breast ◽  
Breast Epithelium ◽  
Normal Breast Epithelium ◽  
Differentially Methylated Genes

Differential DNA methylation is a potential marker of breast cancer risk. Few studies have investigated DNA methylation changes in normal breast tissue and were largely confounded by cancer field effects. To detect methylation changes in normal breast epithelium that are causally associated with breast cancer occurrence, we used a nested case–control study design based on a prospective cohort of patients diagnosed with a primary invasive hormone receptor-positive breast cancer. Twenty patients diagnosed with a contralateral breast cancer (CBC) were matched (1:1) with 20 patients who did not develop a CBC on relevant risk factors. Differentially methylated Cytosine-phosphate-Guanines (CpGs) and regions in normal breast epithelium were identified using an epigenome-wide DNA methylation assay and robust linear regressions. Analyses were replicated in two independent sets of normal breast tissue and blood. We identified 7315 CpGs (FDR < 0.05), 52 passing strict Bonferroni correction (p < 1.22 × 10−7) and 43 mapping to known genes involved in metabolic diseases with significant enrichment (p < 0.01) of pathways involving fatty acids metabolic processes. Four differentially methylated genes were detected in both site-specific and regions analyses (LHX2, TFAP2B, JAKMIP1, SEPT9), and three genes overlapped all three datasets (POM121L2, KCNQ1, CLEC4C). Once validated, the seven differentially methylated genes distinguishing women who developed and who did not develop a sporadic breast cancer could be used to enhance breast cancer risk-stratification, and allow implementation of targeted screening and preventive strategies that would ultimately improve breast cancer prognosis.

The role of low keV virtual monochromatic imaging in increasing the conspicuity of primary breast cancer in dual-energy spectral thoracic CT examination for staging purposes

2019 ◽  
Vol 61 (2) ◽  
pp. 168-174 ◽  
Author(s):  
Yavuz Metin ◽  
Nurgül Orhan Metin ◽  
Oğuzhan Özdemir ◽  
Filiz Taşçı ◽  
Sibel Kul
Keyword(s):  
Breast Cancer ◽  
Primary Breast Cancer ◽  
Breast Tissue ◽  
Normal Breast Tissue ◽  
Energy Levels ◽  
Iodine Content ◽  
Pectoral Muscle ◽  
Dual Energy ◽  
Normal Breast

Background The additive value of dual-energy spectral computerized tomography (DESCT) in breast cancer imaging is still unknown. Purpose To investigate the role of DESCT in improving the conspicuity of primary breast cancer. Material and Methods Twenty-nine patients who were histopathologically diagnosed with breast cancer and underwent DESCT for staging of lung metastasis were evaluated retrospectively. The visual conspicuity of breast cancer was scored by two readers separately in reconstructed virtual monochromatic images obtained at 40, 60, 80, and 100 keV. A circular region of interest slightly smaller than the maximum contrasted portion of the primary breast cancer was manually placed. Iodine enhancement (HU) and iodine content (mg/mL) values of tumor, normal breast tissue and pectoral muscle, and contrast-to-noise values of images at four different energy levels were calculated. Results The lesion conspicuity score peaked at 40-keV series for both readers and was significantly higher than those at other energy levels (all P < 0.001). Lesion iodine enhancement was highest at 40-keV virtual monochromatic image reconstructions ( P < 0.001). The iodine content was significantly higher in tumor than normal breast tissue, and pectoral muscle ( P < 0.001). The highest contrast-to-noise value was obtained at 60 keV (4.0 ± 2.5), followed by 40 keV (3.9 ± 2.2), without a significant difference ( P = 0.33). Conclusion The conspicuity of primary breast cancer was significantly higher in low keV virtual monochromatic images obtained by DESCT. This gives us hope that DESCT may play an effective role in detecting incidental breast lesions. It also raises the question of whether quantitative values obtained by DESCT can be used for characterization of primary breast lesion.

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