scholarly journals Sharp Downregulation of Hub Genes Associated With the Pathogenesis of Breast Cancer From Ductal Carcinoma In Situ to Invasive Ductal Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yao Wang ◽  
Faqing Liang ◽  
Yuting Zhou ◽  
Juanjuan Qiu ◽  
Qing Lv ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Invasive Ductal Carcinoma ◽  
Ductal Carcinoma ◽  
Cancer Tissue ◽  
Hub Genes ◽  
Expression Levels ◽  
Cancer Pathogenesis ◽  
Ductal Hyperplasia

IntroductionBreast atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) are precursor stages of invasive ductal carcinoma (IDC). This study aimed to investigate the pathogenesis of breast cancer by dynamically analyzing expression changes of hub genes from normal mammary epithelium (NME) to simple ductal hyperplasia (SH), ADH, DCIS, and finally to IDC.MethodsLaser-capture microdissection (LCM) data for NME, SH, ADH, DCIS, and IDC cells were obtained. Weighted gene co-expression network analysis (WGCNA) was performed to dynamically analyze the gene modules and hub genes associated with the pathogenesis of breast cancer. Tissue microarray, immunohistochemical, and western blot analyses were performed to determine the protein expression trends of hub genes.ResultsTwo modules showed a trend of increasing expression during the development of breast disease from NME to DCIS, whereas a third module displayed a completely different trend. Interestingly, the three modules displayed inverse trends from DCIS to IDC compared with from NME to DCIS; that is, previously upregulated modules were subsequently downregulated and vice versa. We further analyzed the module that was most closely associated with DCIS (p=7e−07). Kyoto Gene and Genomic Gene Encyclopedia enrichment analysis revealed that the genes in this module were closely related to the cell cycle (p= 4.3e–12). WGCNA revealed eight hub genes in the module, namely, CDK1, NUSAP1, CEP55, TOP2A, MELK, PBK, RRM2, and MAD2L1. Subsequent analysis of these hub genes revealed that their expression levels were lower in IDC tissues than in DCIS tissues, consistent with the expression trend of the module. The protein expression levels of five of the hub genes gradually increased from NME to DCIS and then decreased in IDC. Survival analysis predicted poor survival among breast cancer patients if these hub genes were not downregulated from DCIS to IDC.ConclusionsFive hub genes, RRM2, TOP2A, PBK, MELK, and NUSAP1, which are associated with breast cancer pathogenesis, are gradually upregulated from NME to DCIS and then downregulated in IDC. If these hub genes are not downregulated from DCIS to IDC, patient survival is compromised. However, the underlying mechanisms warrant further elucidation in future studies.

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.

scholarly journals Efficacy of breast MRI for surgical decision in patients with breast cancer: ductal carcinoma in situ versus invasive ductal carcinoma

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jeeyeon Lee ◽  
Jin Hyang Jung ◽  
Wan Wook Kim ◽  
Chan Sub Park ◽  
Ryu Kyung Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Invasive Ductal Carcinoma ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Breast Mri ◽  
Positive Margin ◽  
Breast Conserving Surgery ◽  
Partial Mastectomy

Abstract Background Preoperative breast magnetic resonance imaging (MRI) provides more information than mammography and ultrasonography for determining the surgical plan for patients with breast cancer. This study aimed to determine whether breast MRI is more useful for patients with ductal carcinoma in situ (DCIS) lesions than for those with invasive ductal carcinoma (IDC). Methods A total of 1113 patients with breast cancer underwent mammography, ultrasonography, and additional breast MRI before surgery. The patients were divided into 2 groups: DCIS (n = 199) and IDC (n = 914), and their clinicopathological characteristics and oncological outcomes were compared. Breast surgery was classified as follows: conventional breast-conserving surgery (Group 1), partial mastectomy with volume displacement (Group 2), partial mastectomy with volume replacement (Group 3), and total mastectomy with or without reconstruction (Group 4). The initial surgical plan (based on routine mammography and ultrasonography) and final surgical plan (after additional breast MRI) were compared between the 2 groups. The change in surgical plan was defined as group shifting between the initial and final surgical plans. Results Changes (both increasing and decreasing) in surgical plans were more common in the DCIS group than in the IDC group (P <  0.001). These changes may be attributed to the increased extent of suspicious lesions on breast MRI, detection of additional daughter nodules, multifocality or multicentricity, and suspicious findings on mammography or ultrasonography but benign findings on breast MRI. Furthermore, the positive margin incidence in frozen biopsy was not different (P = 0.138). Conclusions Preoperative breast MRI may provide more information for determining the surgical plan for patients with DCIS than for those with IDC.

scholarly journals Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia

2019 ◽  
Vol 37 (19) ◽  
pp. 1629-1637 ◽  
Author(s):  
Andrea DeCensi ◽  
Matteo Puntoni ◽  
Aliana Guerrieri-Gonzaga ◽  
Silvia Caviglia ◽  
Franca Avino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Intraepithelial Neoplasia ◽  
Hazard Ratio ◽  
Number Needed To Treat ◽  
Ductal Hyperplasia ◽  
Patient Reported

PURPOSE Tamoxifen administered for 5 years at 20 mg/d is effective in breast cancer treatment and prevention, but toxicity has limited its broad use. Biomarker trials showed that 5 mg/d is not inferior to 20 mg/d in decreasing breast cancer proliferation. We hypothesized that a lower dose given for a shorter period could be as effective in preventing recurrence from breast intraepithelial neoplasia but have a lower toxicity than the standard dose. PATIENTS AND METHODS We conducted a multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ. RESULTS Five hundred women 75 years of age or younger were included. After a median follow-up of 5.1 years (interquartile range, 3.9-6.3 years), there were 14 neoplastic events with tamoxifen and 28 with placebo (11.6 v 23.9 per 1,000 person-years; hazard ratio, 0.48; 95% CI, 0.26 to 0.92; P = .02), which resulted in a 5-year number needed to treat of 22 (95% CI, 20 to 27). Tamoxifen decreased contralateral breast events by 75% (three v 12 events; hazard ratio, 0.25; 95% CI, 0.07 to 0.88; P = .02). Patient-reported outcomes were not different between arms except for a slight increase in frequency of daily hot flashes with tamoxifen ( P = .02). There were 12 serious adverse events with tamoxifen and 16 with placebo, including one deep vein thrombosis and one stage I endometrial cancer with tamoxifen and one pulmonary embolism with placebo. CONCLUSION Tamoxifen at 5 mg/d for 3 years can halve the recurrence of breast intraepithelial neoplasia with a limited toxicity, which provides a new treatment option in these disorders.

Differences and Relationships Between Normal and Atypical Ductal Hyperplasia, Ductal Carcinoma In Situ, and Invasive Ductal Carcinoma Tissues in the Breast Based on Raman Spectroscopy

2016 ◽  
Vol 71 (2) ◽  
pp. 300-307 ◽  
Author(s):  
Bing Han ◽  
Ye Du ◽  
Ton Fu ◽  
Zhimin Fan ◽  
Shuping Xu ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Invasive Ductal Carcinoma ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Normal Tissue ◽  
Ductal Carcinoma ◽  
Atypical Ductal Hyperplasia ◽  
Normal Tissues ◽  
Ductal Hyperplasia

The aim of this study was to find the differences and relationships between normal, atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) lesions of the breast based on biochemical characteristics determined by Raman spectroscopy (RS). After collecting 39 frozen sections from patients who underwent surgical resection or mammotome biopsy, nine normal tissues, seven ADH, eight DCIS, and 15 IDC lesions were detected using confocal RS. We then used leave-one-out cross-validation (LOOCV) and radial basis function (RBF) to build a support vector machine (SVM) diagnosis model. Pronounced mean Raman spectra differences were observed between normal tissues, ADH, DCIS, and IDC tissues. Most noticeable was the increased protein and reduced lipid levels of ADH tissues compared to normal tissues. The major spectra differences in ADH, DCIS, and IDC spectrograms were evidenced by a red shift with a broad peak of CH2 (1301 cm−1), the intensity of the stretching vibration peak of carotenoids (1526 cm−1), a relatively strong band of amide-I (1656 cm−1), and the nuclear (882 cm−1) acid peak. Atypical ductal hyperplasia tissues had the largest constituent variations between subjects. During the disease progression, IDC tissues have smaller inter-subject constituent variations than DCIS and ADH tissues. The overall accuracy of SVM model is 74.39%. The sensitivities of normal tissue, ADH, DCIS, and IDC are 62.5%, 50%, 90%, and 66.7%, respectively. The specificities of normal tissue, ADH, DCIS, and IDC are 100%, 100%, 66.7%, and 89.06%, respectively. Atypical ductal hyperplasia shows significant differences and the relationship between normal tissue and malignant disease. Further study to explain the biochemical relationships between these differences will shed more light into a better understanding of the mechanism by which ADH converts to DCIS and to IDC.

scholarly journals Atypical Ductal Hyperplasia after Vacuum-Assisted Breast Biopsy: Can We Reduce the Upgrade to Breast Cancer to an Acceptable Rate?

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1120
Author(s):  
Luca Nicosia ◽  
Antuono Latronico ◽  
Francesca Addante ◽  
Rossella De Santis ◽  
Anna Carla Bozzini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Invasive Carcinoma ◽  
Breast Biopsy ◽  
Ductal Carcinoma ◽  
Atypical Ductal Hyperplasia ◽  
Univariate Analysis ◽  
Surgical Excision ◽  
P Value ◽  
Ductal Hyperplasia

(1) Background: to evaluate which factors can reduce the upgrade rate of atypical ductal hyperplasia (ADH) to in situ or invasive carcinoma in patients who underwent vacuum-assisted breast biopsy (VABB) and subsequent surgical excision. (2) Methods: 2955 VABBs were reviewed; 141 patients with a diagnosis of ADH were selected for subsequent surgical excision. The association between patients’ characteristics and the upgrade rate to breast cancer was evaluated in both univariate and multivariate analyses. (3) Results: the upgrade rates to ductal carcinoma in situ (DCIS) and invasive carcinoma (IC) were, respectively, 29.1% and 7.8%. The pooled upgrade rate to DCIS or IC was statistically lower at univariate analysis, considering the following parameters: complete removal of the lesion (p-value < 0.001); BIRADS ≤ 4a (p-value < 0.001); size of the lesion ≤15 mm (p-value: 0.002); age of the patients <50 years (p-value: 0.035). (4) Conclusions: the overall upgrade rate of ADH to DCIS or IC is high and, as already known, surgery should be recommended. However, ADH cases should always be discussed in multidisciplinary meetings: some parameters appear to be related to a lower upgrade rate. Patients presenting these parameters could be strictly followed up to avoid overtreatment.

scholarly journals Gains and Losses of HLA Class II (DR) and CD4 in Atypical Hyperplasia, Carcinoma in situ and Infiltrating Ductal Carcinoma of the Breast

2004 ◽  
Vol 47 (4) ◽  
pp. 257-262 ◽  
Author(s):  
Demetrio Tamiolakis ◽  
Ioannis Venizelos ◽  
Maria Lambropoulou ◽  
Theodoros Jivannakis ◽  
Evagelia Seliniotaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mhc Class Ii ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Class Ii ◽  
Hla Class Ii ◽  
Cellular Immunotherapy ◽  
Infiltrating Ductal Carcinoma ◽  
Ductal Hyperplasia

Aim: Breast cancer is a frequent cause of death among women with gynaecologic malignancies despite the introduction of combination chemotherapy. There is therefore a need for new therapeutic strategies for patients with breast cancer, such as cellular immunotherapy. In this immunohistochemical study we analyzed the epithelial expression of major histocompatibility complex (MHC) class II (HLA-DR) on atypical and malignant primary mammary epithelial cells, as well as the magnitude of the stromal T lymphocytes (T4 subset) at the tumor site. Experimental design: The study was carried out retrospectively in tumor tissue from 82 patients with mammary lesions (31 cases of atypical ductal hyperplasia -ADH-, 12 cases of ductal carcinoma in situ –DCIS- and 39 cases of infiltrating ductal carcinoma not otherwise specified -IDC-NOS). Medullary carcinomas were not included in our investigation. Material used had been formalin fixed and paraffin embedded. Results: HLA class II (DR) was expressed in 20 of 31 ADHs (64.5%), in 4 of 12 DCISs (33.3%), and in 10 of 39 IDC-NOSs (25.6%). CD4 was expressed in 9 of 31 ADHs (29%), in 5 of 12 DCISs (42%), and in 26 of 39 IDCNOSs (67%). Conclusions: The results showed decreased epithelial expression of HLA class II (DR) and increased stromal expression of CD4, as the lesion progressed to malignancy. Gradual loss of epithelial HLA class II expression might be a manifestation of cellular differentiation from the atypical form versus the malignant one, signaling simultaneously a selective effect on the response capacity of the immune system.

scholarly journals The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ

2021 ◽  
Author(s):  
Abdulbaqi Al-Kawaz ◽  
Islam M. Miligy ◽  
Michael S. Toss ◽  
Omar J. Mohammed ◽  
Andrew R. Green ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Excision Repair ◽  
Prognostic Significance ◽  
Proliferation Index ◽  
Flap Endonuclease 1 ◽  
Cancer Pathogenesis

Abstract Background Impaired DNA repair mechanism is one of the cancer hallmarks. Flap Endonuclease 1 (FEN1) is essential for genomic integrity. FEN1 has key roles during base excision repair (BER) and replication. We hypothesised a role for FEN1 in breast cancer pathogenesis. This study aims to assess the role of FEN1 in breast ductal carcinoma in situ (DCIS). Methods Expression of FEN1 protein was evaluated in a large (n = 1015) well-characterised cohort of DCIS, comprising pure (n = 776) and mixed (DCIS coexists with invasive breast cancer (IBC); n = 239) using immunohistochemistry (IHC). Results FEN1 high expression in DCIS was associated with aggressive and high-risk features including higher nuclear grade, larger tumour size, comedo type necrosis, hormonal receptors negativity, higher proliferation index and triple-negative phenotype. DCIS coexisting with invasive BC showed higher FEN1 nuclear expression compared to normal breast tissue and pure DCIS but revealed significantly lower expression when compared to the invasive component. However, FEN1 protein expression in DCIS was not an independent predictor of local recurrence-free interval. Conclusion High FEN1 expression is linked to features of aggressive tumour behaviour and may play a role in the direct progression of DCIS to invasive disease. Further studies are warranted to evaluate its mechanistic roles in DCIS progression and prognosis.

Semi-quantitative protein analysis of HER2 and ER levels in human breast cancer reveals broad expression ranges within HER2+ and ER+ phenotypes

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11014-11014
Author(s):  
L. Liotta ◽  
M. Pierobon ◽  
J. Wulfkuhle ◽  
J. Laird ◽  
C. Livasy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Human Breast Cancer ◽  
Dynamic Range ◽  
Clinical Laboratory ◽  
Protein Microarray ◽  
Cancer Tissue ◽  
Human Breast ◽  
Expression Levels ◽  
Tissue Specimens

11014 Background: ER and HER2 measurements underpin a majority of breast cancer clinical testing, yet determination of ER and HER2 protein levels are routinely performed using subjective approaches. We have developed a semi-quantitative calibrated protein microarray, the Reverse Phase Protein Microarray (RPMA), to more adequately determine accurate and precise protein expression levels in clinical tissue specimens. We utilized this method to determine HER2 and ER expression levels and compared the results to those values reported from the clinical laboratory. Methods: Pure tumor epithelium from 149 frozen pre-treatment human breast cancer tissue specimens (from the I-SPY TRIAL: CALGB 150007/150012, ACRIN 6657) were procured via Laser Capture Microdissection and protein pathway mapping was performed whereby the ER (N=112) and HER2 (N= 118) levels were directly measured and compared with reported IHC values. Results: Overall, RPMA measurements of HER2 had excellent correlation with IHC and FISH HER2 determination with no IHC or FISH false positives (88/88). 7 out of 30 of the FISH/IHC+ cases were found by RPMA to have HER2 values as low or lower than the FISH/IHC- cases with the HER2+ population having RPMA expression levels that varied by as much as 10-fold. There was less concordance between RPMA ER values and IHC ER values. Detailed analysis of a more homogeneous ER+ population (Allred =8) revealed a large dynamic range of expression of ER (10–20 fold) by RPMA. The HER2 and ER RPMA results were independently validated by Western Blot using a separate biopsy. Conclusions: Discreet protein expression values obtained by RPMA for ER and HER2 reveal distinctly broad expression values, with as much as 10–20 fold dynamic range in expression, even in a homogeneous (e.g. Allred score of 8) population. Such dynamic differences in protein expression may produce dramatic effects in therapeutic response rate. These findings, if found to be clinically useful, point to a potential need for more fine-tuned protein expression determination by quantitative high-throughput technologies for patient stratification even for standard-of-care FDA approved therapies. [Table: see text]

scholarly journals Protein expression of c-erbB-2 and p53 in normal ducts, ductal carcinoma in situ and invasive carcinoma of the same breast

2006 ◽  
Vol 124 (3) ◽  
pp. 121-124 ◽  
Author(s):  
Marcus Vinicius Martins de Menezes ◽  
Anna Letícia Oliveira Cestari ◽  
Orlando Almeida ◽  
Marcelo Alvarenga ◽  
Glauce Aparecida Pinto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Invasive Carcinoma ◽  
Ductal Carcinoma ◽  
P53 Protein ◽  
P53 Protein Expression ◽  
Her 2

CONTEXT AND OBJECTIVE: Breast cancer is thought to derive from progressively aberrant, non-invasive breast lesions, but it is not known exactly how invasive breast cancer develops from these lesions. The aim of this study was to verify the changes in c-erbB-2 and p53 protein expression between non-neoplastic ducts, ductal carcinoma in situ and invasive ductal carcinoma found in the same breast. DESIGN AND SETTING: This was a cross-sectional study at Centro de Atenção Integral à Saúde da Mulher, Campinas, Brazil. METHODS: Fifty-six women with invasive ductal carcinoma and ductal carcinoma in situ in the same breast were included. The expression of c-erbB-2 and p53 proteins was assessed in non-neoplastic and neoplastic cells using immunohistochemical techniques. RESULTS: The c-erbB-2 protein was absent in non-neoplastic ducts but was present in 46% and 36% of in situ and invasive carcinoma components, respectively. Only 2% of non-neoplastic ducts, and 18% and 16% of ductal carcinoma in situ and invasive carcinoma components, respectively, were positive for p53 protein. No significant difference in c-erbB-2 and p53 protein expression was observed between in situ and invasive components. The nuclear grade agreement between in situ and invasive carcinoma was very good. CONCLUSIONS: The invasiveness of ductal carcinoma in situ seems to be independent of the Her-2/neu and TP53 genes. The general features of an occurrence of breast carcinoma are formulated at the outset of carcinogenesis, and the Her-2/neu and TP53 genes are involved.

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