scholarly journals Novel Molecular Markers of Malignancy in Histologically Normal and Benign Breast

2011 ◽  
Vol 2011 ◽  
pp. 1-18 ◽  
Author(s):  
Aejaz Nasir ◽  
Dung-Tsa Chen ◽  
Mike Gruidl ◽  
Evita B. Henderson-Jackson ◽  
Chinnambally Venkataramu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma ◽  
Molecular Classification ◽  
Female Breast Cancer ◽  
Normal Breast ◽  
Molecular Biomarkers ◽  
Low Grade ◽  
Breast Cancer Patients ◽  
Ductal Hyperplasia ◽  
Fresh Frozen

To detect the molecular changes of malignancy in histologically normal breast (HNB) tissues, we recently developed a novel 117-gene-malignancy-signature. Here we report validation of our leading malignancy-risk-genes, topoisomerase-2-alpha (TOP2A), minichromosome-maintenance-protein-2 (MCM2) and “budding-uninhibited-by-benzimidazoles-1-homolog-beta” (BUB1B) at the protein level. Using our 117-gene malignancy-signature, we classified 18 fresh-frozen HNB tissues from 18 adult female breast cancer patients into HNB-tissues with low-grade (HNB-LGMA; ) and high-grade molecular abnormality (HNB-HGMA; ). Archival sections of additional HNB tissues from these patients, and invasive ductal carcinoma (IDC) tissues from six other patients were immunostained for these biomarkers. TOP2A/MCM2 expression was assessed as staining index (%) and BUB1B expression as H-scores (0–300). Increasing TOP2A, MCM2, and BUB1B protein expression from HNB-LGMA to HNB-HGMA tissues to IDCs validated our microarray-based molecular classification of HNB tissues by immunohistochemistry. We also demonstrated an increasing expression of TOP2A protein on an independent test set of HNB/benign/reductionmammoplasties, atypical-ductal-hyperplasia with and without synchronous breast cancer, DCIS and IDC tissues using a custom tissue microarray (TMA). In conclusion, TOP2A, MCM2, and BUB1B proteins are potential molecular biomarkers of malignancy in histologically normal and benign breast tissues. Larger-scale clinical validation studies are needed to further evaluate the clinical utility of these molecular biomarkers.

Histological Assessment of Breast Lesions Identified Exclusively by Magnetic Resonance

2014 ◽  
Vol 80 (10) ◽  
pp. 944-947
Author(s):  
Victoria O'connor ◽  
Elizabeth Arena ◽  
Joslyn Albright ◽  
Nefertiti Brown ◽  
Ryan O'connor ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Magnetic Resonance ◽  
Breast Biopsy ◽  
Ductal Carcinoma ◽  
Low Grade ◽  
Breast Lesions ◽  
Significant Family History ◽  
Ductal Hyperplasia ◽  
Significant Pathology

Radiologic–pathologic correlation of lesions diagnosed by magnetic resonance (MR) is precluded by insufficient data on histological characteristics of lesions suspicious on MR but not visible on concurrent mammogram or ultrasound. The objective of this study was to describe histological features of breast lesions diagnosed exclusively by MR. The participants underwent MR-guided breast biopsy between 2007 and 2012 for a suspicious lesion not identified by mammography or ultrasound. Histology slides were interpreted retrospectively by a breast pathologist. Of 126 patients (126 lesions), 34 (27%) had new breast cancer, 51 (40.5%) previous breast cancer, and 41 (32.5%) dense breasts or a significant family history of breast cancer. MR identified 23 (18.3%) invasive cancers: 20 were Grade 1 and 17 were ductal. Of the 126 lesions, 16 (13%) were ductal carcinoma in situ (DCIS), four were atypical ductal hyperplasia and atypical lobular hyperplasia (3%), and 68 (54%) were benign. Fifteen biopsies (12%) had no significant pathology. Five DCIS lesions were upgraded to T1 invasive cancers. Approximately 30 per cent of suspicious lesions detected exclusively by MR are invasive or in situ cancers that are predominantly low grade. Further studies are needed to determine if malignant lesions can be prospectively distinguished by MR characteristics.

Immunotherapy of Advanced Breast Cancer With a Heterophilic Ganglioside (NeuGcGM3) Cancer Vaccine

2003 ◽  
Vol 21 (6) ◽  
pp. 1015-1021 ◽  
Author(s):  
Adriana Carr ◽  
Edmundo Rodríguez ◽  
María del Carmen Arango ◽  
Rolando Camacho ◽  
Marta Osorio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Vaccine ◽  
Ductal Carcinoma ◽  
Serum Antibody ◽  
World Health ◽  
Stage Iii ◽  
Induction Phase ◽  
Low Grade ◽  
Breast Cancer Patients ◽  
Monthly Basis

Purpose: A heterophilic ganglioside cancer vaccine was developed by combining NeuGcGM3 with the outer membrane protein complex of Neisseria meningitidis to form very small size proteoliposomes (VSSP). A phase I clinical trial was performed to determine safety and immunogenicity of this vaccine. Patients and Methods: Stage III to IV breast cancer patients received up to 15 (200 μg) doses of the vaccine by intramuscular injection. The first five doses (induction phase) were given at 2-week intervals, with the remaining treatment (maintenance) administered on a monthly basis. Results: Twenty-one patients, 11 of whom had metastatic disease, were included. Main toxicities included erythema and induration at the injection site, sometimes associated with mild pain, and low-grade fever (World Health Organization grades 1 and 2). All treated patients who completed the induction phase developed anti-NeuGcGM3 antibody titers between 1:1,280 and 1:164,000 immunoglobulin G (IgG), and 1:640 and 1:164,000 IgM. Noteworthy specific IgA antibodies were induced by vaccination in all stage III patients and in three stage IV patients. Serum antibody levels were higher in the stage III patients, with the larger increases observed after week 32. The antiganglioside IgG subclasses were mainly IgG1 and IgG3. Hyperimmune sera increased complement-mediated cytotoxicity versus P3X63 myeloma cells and a marked IgG differential reactivity against human mammary ductal carcinoma samples. Conclusion: NeuGcGM3/VSSP/Montanide ISA 51 is an unusual immunogenic ganglioside vaccine and also seems to be safe in this small trial. Immunologic surrogates of activity indicate that this reagent warrants further investigation.

scholarly journals Expression of Malic Enzyme 3 in Breast Cancer and Precancerous Lesions: a Promising Novel Biomarker for Carcinogenesis and Prognosis

2021 ◽  
Author(s):  
Duo You ◽  
Danfeng Du ◽  
Xinmin Li ◽  
Xun Hu
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Precancerous Lesions ◽  
Characteristic Curve ◽  
Tnm Staging ◽  
Normal Breast ◽  
Breast Cancer Patients ◽  
Usual Ductal Hyperplasia ◽  
Ductal Hyperplasia ◽  
Positive Immunostaining

Abstract Purpose: While malic enzymes 1 (ME1) was correlated with breast cancer progression and prognosis, the association of ME3 (a homologue of ME1) with breast cancer is not known. The aim of this study is to explore the potential of ME3 as a biomarker in breast cancer carcinogenesis and prognosis.Methods: A total of 107 patients confirmed with breast cancer were enrolled. The ME3 expression was evaluated by IHC and correlated with clinicopathological indicators.Results: The ME3 positive immunostaining rate was higher in normal breast tissues and decreased stepwise from normal (97.60%) to usual ductal hyperplasia (91.1%), atypical ductal hyperplasia (64.2%), carcinoma in situ (62.5%) and invasive carcinoma (45.5%). Similarly, the decreasing tendency was observed for ME3 positive immunostaining rate from Tis (75.0%) through T1 (62.5%) and T2 (37.5%) to T3 (33.3%) and from stag 0 (75.0%) through I (72.0%), II (44.4%) to III (24.1%). ME3 expression was related with negative lymph node metastasis. Patients with positive expression of ME3 had better outcome. By incorporating ME3 into tumor TNM staging, the area under receiver operating characteristic curve for the 5-year survival was increased from 84.0% to 87.5%. Conclusions: ME3 may be a promising biomarker for better prognosis for breast cancer patients.

scholarly journals Matriptase and Survivin Expression Associated with Tumor Progression and Malignant Potential in Breast Cancer of Chinese Women: Tissue Microarray Analysis of Immunostaining Scores with Clinicopathological Parameters

2008 ◽  
Vol 24 (2) ◽  
pp. 89-99 ◽  
Author(s):  
Wen-Chiuan Tsai ◽  
Chi-Hong Chu ◽  
Cheng-Pin Yu ◽  
Lai-Fa Sheu ◽  
Ann Chen ◽  
...  
Keyword(s):  
Invasive Ductal Carcinoma ◽  
Ductal Carcinoma ◽  
Survivin Expression ◽  
Normal Breast ◽  
Clinicopathological Parameters ◽  
Low Grade ◽  
High Grade ◽  
Ductal Hyperplasia ◽  
Grade Ii ◽  
Grade Iii

Objective: The aim of this study was to examine the expression of matriptase and survivin in breast carcinoma and correlate with clinicopathological parameters.Methods: Immunohistochemical analysis of matriptase and survivin were performed in tissue microarray slides of 290 cases, including 11 normal breast tissue; 27 fibrocystic disease; 17 fibroadenoma; 6 atypical ductal hyperplasia; 39 ductal carcinoma in situ, low grade (DCIS, low grade); 39 ductal carcinoma in situ, high grade (DCIS, high grade); 27 invasive ductal carcinoma, grade I (IDC, grade I); 78 invasive ductal carcinoma, grade II (IDC, grade II); and 46 invasive ductal carcinoma, grade III (IDC, grade III).Results: The average immunostaining scores of matriptase were 44.1 in normal breast tissue, 52.7 in fibrocystic disease, 76.5 in fibroadenoma, 81.7 in atypical ductal hyperplasia, 133.7 in low-grade DCIS, and 155.8 in high-grade DCIS. Among 151 breast IDC cases, the average immunostaining scores of matriptase were 172.7 in grade I, 211.7 in grade II, and 221.2 in grade III. Additionally, the average immunostaining scores of surviving also correlate with tumor grades and stages.Conclusions: Higher expressions of matriptase and survivin correlate significantly with clinicopathological parameters in breast cancer and the malignant potential in premalignant lesions. In addition, higher survivin expression had poorer prognosis of breast IDC cases.

scholarly journals Upregulation of miR-21 and miR-106b in plasma and tissues as a possible prognostic marker in aggressive breast cancer

2021 ◽  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma ◽  
Reduction Mammoplasty ◽  
Lymph Node Involvement ◽  
Normal Breast ◽  
Cancer Prognosis ◽  
Mammary Tissue ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Breast Tissues

Background: The miRNAs are referred to small non-coding RNAs (consisting of 18 to 25 nucleotides). Functional studies have shown their functions to be oncogenes or tumor suppressor genes in different types of cancers. The miR-106b and miR-21 have been identified to participate in the biological behaviors of cells. This study aimed to evaluate the tissue and plasma levels of miR-21 and miR-106b in patients with breast cancer who were diagnosed with ductal carcinoma. Methods: In total, 40 cases of breast cancer patients 180 samples were examined in this project. Samples included ductal carcinoma breast tumors (n=40), normal breast tissues of the margin of the tumor (n=40) and 20 samples from unaffected mammary tissue of females undergoing reduction mammoplasty (control group), plasma samples of patients with breast cancer (n=40), and plasma of non-affected individuals (n=40). The expression levels of miR-106b and miR-21 were determined using SYBR Green real-time RT-PCR assay in breast tissues and plasma of cancerous patients in comparison to the controls. Results: MiR-106b and miR-21 revealed much higher expression in tissues and plasma of patients with breast cancer in comparison to that in the group of control (P<0.001). High levels of mir-106b and miR-21 expression in plasma and tumor tissues were highly correlated with tumors in higher stages and lymph node involvement (P<0.0001). Conclusions: Based on the obtained results, upregulation of miR-106b and miR-21 in the plasma of patients with breast cancer can act as a possible non-invasive biomarker for breast cancer prognosis. Further follow-up studies are required to confirm this.

scholarly journals Open Surgical Biopsy in Diagnosis of Mammographically Detected Suspicious Microcalcifications

2018 ◽  
Vol 49 (2) ◽  
Author(s):  
Aleksandar Guzijan ◽  
Dragana Roganović ◽  
Danijela Soprenić
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma ◽  
Radial Scar ◽  
Low Grade ◽  
Surgical Biopsy ◽  
Ductal Hyperplasia ◽  
Open Surgical Biopsy ◽  
Premalignant Condition ◽  
Specimen Radiography

Background: One of the earliest signs of breast cancer may be the presence of mammographically detected suspicious microcalcifications in the breast. The aim of the study was to present an open surgical biopsy of the mammographically detected suspicious microcalcifications in a breast, with preoperative wire marking of the lesions and intraoperative specimen radiography, as a reliable and valid procedure.Material and Methods: The study included 80 female patients underwent surgery because of mammographically detected suspicious microcalcifications. The method of preoperative ultrasound-guided wire marking of a zone of microcalcification was performed in all patients.After wire marking, the control native mammography in ML and CC projections was performed, in order to locate the microcalcifications relative to the wire. In all patients, the extirpation of the suspicious microcalcifications was verified by the specimen radiography.Results: In the definitive histopathological finding in situ component of ductal carcinoma of the breast was verified in nine (11,25%) examinees. High grade in situ component was verified in eight (10%) examinees and low grade in situ component in one examinee (1,25%). In 11 (13,75%) examinees, the invasive breast cancer with an extensive in situ component up to 50% was verified. In 46 (57,5%) of the examinees, benign, non-proliferative changes were verified, while proliferative changes characterized as premalignant condition (sclerosing adenosis, radial scar and atypical ductal hyperplasia) were verified in 14 (17,5%) examinees. Microcalcifications verified by specimen radiography are completely removed.Conclusion: Presence of mammographically detected suspicious microcalcifications has a significant predictive value in the early detection of breast cancer. The method of an open surgical biopsy, as an alternative to stereotactic biopsy, is valid in diagnostic of the mammographically suspicious microcalcifications.

Treatment disparities in female breast cancer patients according to race, ethnicity and socioeconomic status

2013 ◽  
Author(s):  
Christopher S. Bartlett ◽  
Tulay Koru-Sengul ◽  
Feng Miao ◽  
Stacey L. Tannenbaum ◽  
David J. Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Socioeconomic Status ◽  
Cancer Patients ◽  
Female Breast Cancer ◽  
Breast Cancer Patients ◽  
Female Breast ◽  
Treatment Disparities ◽  
Race Ethnicity
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