Lymphovascular invasion and histologic grade are associated with specific genomic profiles in invasive carcinomas of the breast

Fidalgo, Felipe; Rodrigues, T.; Pinilla, Mabel G.; Silva, Amanda Gonçalves da; Maciel, Maria do Socorro; Rosenberg, Carla; Andrade, Victor Piana de; Carraro, Dirce Maria; Krepischi, Ana Cristina Victorino

doi:10.1007/s13277-014-2786-z

Cited by 25 publications

(24 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The DCIS lesions in cluster A that correlates with high NG may be more progression-prone to IDC than those in cluster B. This is consistent with the previous notion that NG largely paralleled the total number of gene CNAs and the risk of progression from DCIS to IDC [31, 35]. …”

Section: Discussionsupporting

confidence: 88%

Progression Potential of Ductal Carcinoma in situ Assessed by Genomic Copy Number Profiling

et al. 2018

View full text Add to dashboard Cite

Background: Ductal carcinoma in situ (DCIS) of the breast is heterogeneous in terms of the risk of progression to invasive ductal carcinoma (IDC). To treat DCIS appropriately for its progression risk, we classified individual DCIS by its profile of genomic changes into 2 groups and correlated them with clinicopathological progression factors. Methods: We used surgically resected, formalin-fixed, paraffin-embedded tissues of 22 DCIS and 30 IDC lesions. We performed immunohistochemical intrinsic subtyping, array-based comparative genomic hybridization, and unsupervised clustering. Results: The samples were divided into 2 major clusters, A and B. Cluster A showed a greater number of gene and chromosome copy number alterations, a larger IDC/DCIS ratio, a higher frequency of nonluminal subtype, a lower frequency of luminal subtype, and a higher nuclear grade, when compared with cluster B. However, there was no difference in the frequencies of lymph node metastasis between clusters A and B. We identified 9 breast-cancer-related genes, including TP53 and GATA3, that highly contributed to the discrimination of A and B clusters. Conclusion: Classification of breast tumors into rapidly progressive cluster A and the other (cluster B) may contribute to select the treatment appropriate for their progression risk.

show abstract

Section: Discussionsupporting

confidence: 88%

Progression Potential of Ductal Carcinoma in situ Assessed by Genomic Copy Number Profiling

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Stromal cells assist in proteolytic degradation via matrix metalloproteinase (MMP) dictated by the epigenetic regulations from malignant cells. Strong correlations have been reported between LVI and MMP9 [50,51] and MMP1 expression [52]. Overexpression of cancer cell-associated membrane type-1 (MT1)-MMP by BC cells has been reported to induce degradation of the vascular basement membrane and cancer cell intravasation [53].…”

Section: Tumour Cell Invasiveness Tumour Microenvironment and LVImentioning

confidence: 99%

“…CD24, CDKN3, UBE2C and PIK3R1 , play a role in BC development and progression [77]. In a recent study, Fidalgo et al [78] applied array-CGH, RT-qPCR and cDNA micro-arrays to identify DNA copy number aberrations and the gene expression profile linked to LVI in a cohort of invasive BC. Although they did not find a significant association between LVI and increased genomic instability considering the total number of chromosomal alterations, they identified an increased frequency of specific alterations associated with LVI, including gains at 5p, 16p, 17q12 and 19, and losses at 8p, 11q, 18q and 21.…”

Section: Gene Expression Profiling Gene Signatures and LVImentioning

confidence: 99%

“…They also detected three novel small-scale rearrangements in LVI-positive grade 3 tumours that harbour putative BC genes, including amplicons at 11p11.2 (harbouring HSD17B12 ), 20q13.2 (harbouring ZNF217 ), 19q12 (harbouring CCNE1 ) and 4q13.3 (harbouring ADAMTS3 ), and a deletion at 12p12.3 (harbouring RERGL and PIK3C2G ). Gene expression analysis revealed networks highlighting MMP1 , MED1 and S100A8 as potential candidate genes involved in LVI-positive grade 3 tumours [78]. Genes that showed a concordant pattern of up-regulated gene expression and copy number gains/high gains in LVI-positive samples were UMOD , ARSG , MYCBPAP and MED1 [78].…”

Section: Gene Expression Profiling Gene Signatures and LVImentioning

confidence: 99%

“…Gene expression analysis revealed networks highlighting MMP1 , MED1 and S100A8 as potential candidate genes involved in LVI-positive grade 3 tumours [78]. Genes that showed a concordant pattern of up-regulated gene expression and copy number gains/high gains in LVI-positive samples were UMOD , ARSG , MYCBPAP and MED1 [78]. Despite the promising results of this study, it is important to note that the cohort of BC was small (n = 57), and frozen tissue was utilized with no further validation of LVI status.…”

Section: Gene Expression Profiling Gene Signatures and LVImentioning

confidence: 99%

See 2 more Smart Citations

Molecular Mechanisms Underlying Lymphovascular Invasion in Invasive Breast Cancer

et al. 2015

View full text Add to dashboard Cite

Lymphovascular invasion (LVI), the presence of malignant cells within lymphovascular channels, is a crucial step in the invasion-metastasis cascade. LVI, when identified morphologically in the peritumoural area, is regarded as an indicator of metastatic potential and is strongly associated with a poor prognosis in many solid tumours, including breast cancer (BC). Although molecular mechanisms associated with the development of LVI have been extensively studied, details of driver genes, and molecular pathways and mechanisms involved in its development in BC, remain poorly defined. Although invasive BC cells have the ability to invade surrounding stroma, only those that can interact with endothelial cells, penetrate the vascular wall and withstand the intravascular stress will develop LVI and complete metastatic dissemination. Identification of additional molecular events associated with LVI in the primary tumour and characterisation of the contribution of the tumour micro-environment to modulating biological processes leading to LVI in BC remain a challenging task. This stems not only from the complexity of the molecular alterations in the primary tumour and the interactions with different components of its micro-environment but also from the subjective nature of LVI assessment in human BC. In this review, we discuss the clinicopathological features and the current knowledge of the molecular mechanisms underlying LVI in BC.

show abstract

The molecular basis of breast cancer pathological phenotypes

et al. 2016

View full text Add to dashboard Cite

The histopathological evaluation of morphological features in breast tumours provides prognostic information to guide therapy. Adjunct molecular analyses provide further diagnostic, prognostic and predictive information. However, there is limited knowledge of the molecular basis of morphological phenotypes in invasive breast cancer. This study integrated genomic, transcriptomic and protein data to provide a comprehensive molecular profiling of morphological features in breast cancer. Fifteen pathologists assessed 850 invasive breast cancer cases from The Cancer Genome Atlas (TCGA). Morphological features were significantly associated with genomic alteration, DNA methylation subtype, PAM50 and microRNA subtypes, proliferation scores, gene expression and/or reverse-phase protein assay subtype. Marked nuclear pleomorphism, necrosis, inflammation and a high mitotic count were associated with the basal-like subtype, and had a similar molecular basis. Omics-based signatures were constructed to predict morphological features. The association of morphology transcriptome signatures with overall survival in oestrogen receptor (ER)-positive and ER-negative breast cancer was first assessed by use of the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset; signatures that remained prognostic in the METABRIC multivariate analysis were further evaluated in five additional datasets. The transcriptomic signature of poorly differentiated epithelial tubules was prognostic in ER-positive breast cancer. No signature was prognostic in ER-negative breast cancer. This study provided new insights into the molecular basis of breast cancer morphological phenotypes. The integration of morphological with molecular data has the potential to refine breast cancer classification, predict response to therapy, enhance our understanding of breast cancer biology, and improve clinical management. This work is publicly accessible at www.dx.ai/tcga_breast.

show abstract

Lymphovascular invasion and histologic grade are associated with specific genomic profiles in invasive carcinomas of the breast

Cited by 25 publications

References 64 publications

Progression Potential of Ductal Carcinoma in situ Assessed by Genomic Copy Number Profiling

Progression Potential of Ductal Carcinoma in situ Assessed by Genomic Copy Number Profiling

Molecular Mechanisms Underlying Lymphovascular Invasion in Invasive Breast Cancer

The molecular basis of breast cancer pathological phenotypes

Contact Info

Product

Resources

About