scholarly journals Genetic Alterations in Presumptive Precursor Lesions of Breast Carcinomas

2002 ◽  
Vol 24 (2-3) ◽  
pp. 69-76 ◽  
Author(s):  
Michaela Aubele ◽  
Martin Werner ◽  
Heinz Höfler
Keyword(s):  
Ductal Carcinoma ◽  
Early Stage ◽  
Dna Amplification ◽  
Genetic Alterations ◽  
Molecular Genetic Analysis ◽  
Premalignant Lesions ◽  
Comparative Genomic ◽  
Precursor Lesions ◽  
Normal Epithelium

The hypothetical multistep model of breast carcinogenesis suggests a transition from normal epithelium to invasive carcinoma via intraductal hyperplasia (without and with atypia) andin situcarcinoma. These presumptive precursor lesions are currently defined by their histological features, and their prognosis is imprecisely estimated from indirect epidemiological evidence. Cytogenetic and molecular‐genetic analysis of these lesions give evidence for an accumulation of various genetic alterations during breast tumorigenesis. Using immuno‐histochemistry overexpression of the c‐erbB‐2 oncogene was found in ductal carcinomain situ(DCIS), but not in atypical intraductal hyperplasia (AIDH) and intraductal hyperplasia (IDH). An expression of mutant p53 tumor suppressor gene as well as expression of cyclin D1 was identified in DCIS. In IDH lesions loss of heterozygosity (LOH) at various loci could be identified, and comparative genomic hybridization (CGH) and fluorescencein situhybridization (FISH) studies delivered evidence for DNA amplification on chromosomal region 20q13 in the early stage of IDH. However, little is currently known about genetic alterations in those premalignant lesions, and the chronology of genetic alterations and histopathological changes during carcinogenesis is mainly undiscovered. Figure 1 can be viewed in colour onhttp://www.esacp.org/acp/2002/24‐23/aubele.htm

scholarly journals A Biphasic Pleural Tumor with Features of an Epithelioid and Small Cell Mesothelioma: Morphologic and Molecular Findings

2016 ◽  
Vol 2016 ◽  
pp. 1-10
Author(s):  
Sarah Hackman ◽  
Richard D. Hammer ◽  
Lester Layfield
Keyword(s):  
Abdominal Cavity ◽  
Molecular Genetic ◽  
Genetic Alterations ◽  
Small Cell ◽  
Comparative Genomic ◽  
Cell Nuclei ◽  
Pleural Tumor ◽  
Young Males ◽  
Round Cell Tumors

Malignant mesotheliomas are generally classified into epithelioid, sarcomatoid, desmoplastic, and biphasic types with rare reports of a small cell form. These small cell variants display some morphologic overlap with desmoplastic small round cell tumors (DSRCTs) which generally occur within the abdominal cavity of young males and are defined by a characteristic t(11;22)(p13;q12) translocation. However, there are rare reports of DSRCTs lacking this translocation. We present a 78-year-old man with a pleura-based biphasic neoplasm with features of both epithelioid mesothelioma and a small cell blastema-like neoplasm. The epithelioid portion showed IHC reactivity for pan cytokeratin, CK5/6, D2-40, and calretinin and the small cell portion marked with CD99, pan cytokeratin, WT1, FLI1, S100, CD200, MyoD1, and CD15. Fluorescence in situ hybridization testing for the t(11;22)(p13;q12) translocation disclosed loss of theEWSR1gene in 94% of tumor cell nuclei, but there was no evidence of the classic translocation. Array based-comparative genomic hybridization (a-CGH) confirmed the tumor had numerous chromosome copy number losses, including 11p15.5-p11.12 and 22q12.1-q13.33, with loss of theEWSR1andWT1gene regions. Herein, we report novel complex CGH findings in a biphasic tumor and review the molecular genetic alterations in both mesothelioma and DSRCTs.

Atypical cystic lobules: an early stage in the formation of low-grade ductal carcinoma in situ

1999 ◽  
Vol 435 (4) ◽  
pp. 413-421 ◽  
Author(s):  
Tetsunari Oyama ◽  
Horacio Maluf ◽  
F. Koerner
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Low Grade

Relationship of Breast Magnetic Resonance Imaging to Outcome After Breast-Conservation Treatment With Radiation for Women With Early-Stage Invasive Breast Carcinoma or Ductal Carcinoma in Situ

2008 ◽  
Vol 26 (3) ◽  
pp. 386-391 ◽  
Author(s):  
Lawrence J. Solin ◽  
Susan G. Orel ◽  
Wei-Ting Hwang ◽  
Eleanor E. Harris ◽  
Mitchell D. Schnall
Keyword(s):  
Breast Carcinoma ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Breast Mri ◽  
Invasive Breast Carcinoma ◽  
Breast Conservation Treatment ◽  
Mri Study

Purpose To determine the relationship of breast magnetic resonance imaging (MRI) to outcome after breast-conservation treatment (BCT) with radiation for women with early-stage invasive breast carcinoma or ductal carcinoma in situ. Patients and Methods A total of 756 women with early stage invasive breast carcinoma or ductal carcinoma in situ underwent BCT including definitive breast irradiation during 1992 to 2001. At the time of initial diagnosis and evaluation, routine breast imaging included conventional mammography. Of the 756 women, 215 women (28%) had also undergone a breast MRI study, and 541 women (72%) had not undergone a breast MRI study. The median follow-up after treatment was 4.6 years (range, 0.1 to 13.5 years). Results For the women with a breast MRI study compared with the women without a breast MRI study, there were no differences in the 8-year rates of any local failure (3% v 4%, respectively; P = .51) or local-only first failure (3% v 4%, respectively; P = .32). There were also no differences between the two groups for the 8-year rates of overall survival (86% v 87%, respectively; P = .51), cause-specific survival (94% v 95%, respectively; P = .63), freedom from distant metastases (89% v 92%, respectively; P = .16), or contralateral breast cancer (6% v 6%, respectively; P = .39). Conclusion The use of a breast MRI study at the time of initial diagnosis and evaluation was not associated with an improvement in outcome after BCT with radiation.

scholarly journals DCIS genomic signatures define biology and correlate with clinical outcome: a Human Tumor Atlas Network (HTAN) analysis of TBCRC 038 and RAHBT cohorts

2021 ◽  
Author(s):  
Siri H Strand ◽  
Belen Rivero-Gutierrez ◽  
Kathleen E Houlahan ◽  
Jose A Seoane ◽  
Lorraine King ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Immune Cell ◽  
De Novo ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Expression Patterns ◽  
Human Tumor ◽  
Multiscale Approach

Ductal carcinoma in situ (DCIS) is the most common precursor of invasive breast cancer (IBC), with variable propensity for progression. We have performed the first multiscale, integrated profiling of DCIS with clinical outcomes by analyzing 677 DCIS samples from 481 patients with 7.1 years median follow-up from the Translational Breast Cancer Research Consortium (TBCRC) 038 study and the Resource of Archival Breast Tissue (RAHBT) cohorts. We made observations on DNA, RNA, and protein expression, and generated a de novo clustering scheme for DCIS that represents a fundamental transcriptomic organization at this early stage of breast neoplasia. Distinct stromal expression patterns and immune cell compositions were identified. We found RNA expression patterns that correlate with later events. Our multiscale approach employed in situ methods to generate a spatially resolved atlas of breast precancers, where complementary modalities can be directly compared and correlated with conventional pathology findings, disease states, and clinical outcome.

scholarly journals The breast pre-cancer atlas illustrates the molecular and micro-environmental diversity of ductal carcinoma in situ

2021 ◽  
Author(s):  
Daniela Nachmanson ◽  
Adam Officer ◽  
Hidetoshi Mori ◽  
Jonathan Gordon ◽  
Mark F. Evans ◽  
...  
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Prognostic Models ◽  
Low Grade ◽  
High Grade ◽  
Luminal A ◽  
Environmental Diversity

The increased detection and treatment of early stage breast cancer as well as ductal carcinoma in situ (DCIS) has not led to significant survival benefits. Therefore, the current standard treatment of DCIS is questionable. An informed evidence-based treatment strategy, and likely de-escalation from the current standards requires new prognostic models built from more comprehensive characterization with objective criteria. Parallel profiling of the molecular landscape and micro-environment in pure DCIS remains challenging due to histological heterogeneity and the inevitable reliance on small archived specimens. Leveraging recent methodological advances, we characterized the mutational, transcriptional, histological and microenvironmental landscape across multiple micro-dissected regions from 39 cases to generate a multi-modal breast precancer atlas. The histological architecture was associated with grade, adiposity, and intrinsic expression subtypes. Similar to previous findings, high-grade lesions had higher mutational burden, including TP53 mutations, while low-grade lesions had more frequent 16q losses and GATA3 mutations. Multi-region analysis revealed most somatic alterations, including whole genome duplication events, were clonal, but genetic divergence increased with distance between regions. In 7/12 evaluable cases, somatic mutations in putative driver genes affected a subset of regions only. This genetic heterogeneity often accompanied phenotypic heterogeneity and regions with low risk features (Normal-like, Luminal A) occurred earlier than those with high-risk features (Her2-like, Basal or necrosis) according to the phylogenetic analysis. The immune-environment was evaluated using multiplex immuno-histochemistry to measure relative stromal and epithelial densities of B lymphocyte (B-cell), T lymphocyte (T-cell) and regulatory T cells (T-reg) and identify 3 immune-states: Active, Suppressed and Excluded (lower epithelial density). All states included both DCIS and adjacent benign regions, and none associated with intrinsic subtypes. The Excluded state was enriched in high-grade DCIS and, compared to benign areas, more likely acquired in DCIS, showing transcriptional evidence of stronger immune-suppression and possible evasion. The breast pre-cancer atlas therefore reveals correlated levels of phenotypic and genotypic heterogeneity, including at sub-histological resolution. These uniquely integrated observations will help scope future studies, prioritize candidate markers for progression risk modelling and identify functional similarities in precursor lesions from other types of adenocarcinomas.

Long-term risk of second malignancies in women with ductal carcinoma in situ or early-stage invasive breast cancer after breast conservation treatment.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12103-e12103
Author(s):  
Carolyn J. Kushner ◽  
Wei-Ting Hwang ◽  
Lawrence J. Solin ◽  
Neha Vapiwala
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Breast Conservation ◽  
Conservation Treatment ◽  
Breast Conservation Treatment

e12103 Background: Women with ductal carcinoma in situ (DCIS) or early stage breast cancer have a good prognosis after breast conservation treatment (BCT), and are at risk for second malignant neoplasms (SMNs). The long-term risk of SMNs is not well established and carries important public health implications. Methods: A total of 755 women with DCIS or stage I-II invasive breast cancer underwent breast-conserving surgery followed by definitive breast irradiation between 1995 and 2001. Systemic therapy (chemotherapy and/or hormonal therapy) was given to 73% of the patients. We have previously described patient demographics and 15-year oncologic outcomes in detail (Vapiwala, Cancer, 2017). The patient records were reviewed for development of SMNs. SMNs of any anatomic site (other than contralateral breast cancer and basal/squamous cell carcinoma of the skin) were included for analysis. The Kaplan-Meier method was used to determine the rate of SMNs over time. Median follow-up was 13.8 years. Results: The 5-, 10-, and 15-year rates of developing any SMN were 3.6% (95% CI 2.4-5.3%), 7.8% (95% CI 6.0-10.2%), and 12.7% (95% CI 10.2-15.8%). The most common SMNs were uterine (n=12), leukemia/lymphoma (n=11), melanoma (n=10), ovarian (n=9), and lung (n=7). Conclusions: Development of SMNs is a substantial risk for a protracted period of time following BCT. Clinical patterns of specific SMN histologies, locations and time course of development suggest potential opportunities for screening and treatment to guide patient survivorship clinics and protocols.

scholarly journals SMARCE1 is required for the invasive progression of in situ cancers

2017 ◽  
Vol 114 (16) ◽  
pp. 4153-4158 ◽  
Author(s):  
Ethan S. Sokol ◽  
Yu-Xiong Feng ◽  
Dexter X. Jin ◽  
Minu D. Tizabi ◽  
Daniel H. Miller ◽  
...  
Keyword(s):  
Ductal Carcinoma ◽  
Early Stage ◽  
Strong Predictor ◽  
Breast Lesions ◽  
Functional Studies ◽  
Exponential Increase ◽  
Key Driver ◽  
Secreted Proteases

Advances in mammography have sparked an exponential increase in the detection of early-stage breast lesions, most commonly ductal carcinoma in situ (DCIS). More than 50% of DCIS lesions are benign and will remain indolent, never progressing to invasive cancers. However, the factors that promote DCIS invasion remain poorly understood. Here, we show that SMARCE1 is required for the invasive progression of DCIS and other early-stage tumors. We show that SMARCE1 drives invasion by regulating the expression of secreted proteases that degrade basement membrane, an ECM barrier surrounding all epithelial tissues. In functional studies, SMARCE1 promotes invasion of in situ cancers growing within primary human mammary tissues and is also required for metastasis in vivo. Mechanistically, SMARCE1 drives invasion by forming a SWI/SNF-independent complex with the transcription factor ILF3. In patients diagnosed with early-stage cancers, SMARCE1 expression is a strong predictor of eventual relapse and metastasis. Collectively, these findings establish SMARCE1 as a key driver of invasive progression in early-stage tumors.

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