Molecular markers of breast axillary lymph node metastasis

Cavalli, Luciane R.

doi:10.1586/erm.09.30

Cited by 19 publications

(19 citation statements)

References 181 publications

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“…4,18,37,38 Several other breast cancer markers have been associated with axillary lymph node metastasis such as CCND1, CD44, COX-2, EGFR, HER2/NEU, HPA, and LYVE-1 (reviewed in Ref. 39). In addition, increased expression of vascular endothelial growth factor C (VEGF-C) or VEGF-A, both of which are able to promote lymphangiogenesis in primary tumors, was correlated with an increased incidence of regional lymph node as well as distant metastases in humans and animals.…”

Section: Discussionmentioning

confidence: 99%

“…[30][31][32] Different techniques assessing protein expression, mRNA expression, chromosome alterations, and DNA copy number changes are being used to evaluate these markers of lymph node metastasis in primary breast tumors. 39 The advantage of SHG detection of Col1 fibers as a biomarker of lymph node metastasis is that the technique is nondestructive and can be used to interrogate live tissues.…”

Section: Discussionmentioning

confidence: 99%

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Collagen I fiber density increases in lymph node positive breast cancers: pilot study

et al. 2012

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Abstract. Collagen I (Col1) fibers are a major structural component in the extracellular matrix of human breast cancers. In a preliminary pilot study, we explored the link between Col1 fiber density in primary human breast cancers and the occurrence of lymph node metastasis. Col1 fibers were detected by second harmonic generation (SHG) microscopy in primary human breast cancers from patients presenting with lymph node metastasis (LN þ ) versus those without lymph node metastasis (LN − ). Col1 fiber density, which was quantified using our in-house SHG image analysis software, was significantly higher in the primary human breast cancers of LN þ (fiber volume ¼ 29.22% AE 4.72%, inter-fiber distance ¼ 2.25 AE 0.45 μm) versus LN − (fiber volume ¼ 20.33%AE 5.56%, inter-fiber distance ¼ 2.88 AE 1.07 μm) patients. Texture analysis by evaluating the co-occurrence matrix and the Fourier transform of the Col1 fibers proved to be significantly different for the parameters of co-relation and energy, as well as aspect ratio and eccentricity, for LN þ versus LN − cases. We also demonstrated that tissue fixation and paraffin embedding had negligible effect on SHG Col1 fiber detection and quantification. High Col1 fiber density in primary breast tumors is associated with breast cancer metastasis and may serve as an imaging biomarker of metastasis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Collagen I fiber density increases in lymph node positive breast cancers: pilot study

et al. 2012

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“…However, most of these prognostic and predictive models have been developed based on primary tumor tissue, whereas metastases, rather than the primary tumor, determine the clinical outcome of cancer patients. It has been shown that metastases, which may develop several years after occurrence of the primary tumor and after prior systemic therapy in the adjuvant or neoadjuvant setting, can differ greatly from primary tumor tissue in terms of genetic characteristics (7)(8)(9)(10)(11)(12)(13). It is therefore anticipated that molecular characterization of metastases will improve the currently available prognostic and predictive models.…”

Section: Introductionmentioning

confidence: 99%

mRNA and microRNA Expression Profiles in Circulating Tumor Cells and Primary Tumors of Metastatic Breast Cancer Patients

Sieuwerts

Mostert

Vries

et al. 2011

Clinical Cancer Research

208

158

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Purpose: Molecular characterization of circulating tumor cells (CTC) holds great promise. Unfortunately, routinely isolated CTC fractions currently still contain contaminating leukocytes, which makes CTC-specific molecular characterization extremely challenging. In this study, we determined mRNA and microRNA (miRNA) expression of potentially CTC-specific genes that are considered to be clinically relevant in breast cancer.Experimental Design: CTCs were isolated with the epithelial cell adhesion molecule-based CellSearch Profile Kit. Selected genes were measured by real-time reverse transcriptase PCR in CTCs of 50 metastatic breast cancer patients collected before starting first-line systemic therapy in blood from 53 healthy blood donors (HBD) and in primary tumors of 8 of the patients. The molecular profiles were associated with CTC counts and clinical parameters and compared with the profiles generated from the corresponding primary tumors.Results: We identified 55 mRNAs and 10 miRNAs more abundantly expressed in samples from 32 patients with at least 5 CTCs in 7.5 mL of blood compared with samples from 9 patients without detectable CTCs and HBDs. Clustering analysis resulted in 4 different patient clusters characterized by 5 distinct gene clusters. Twice the number of patients from cluster 2 to 4 had developed both visceral and nonvisceral metastases. Comparing transcript levels in CTCs with those measured in corresponding primary tumors showed clinically relevant discrepancies in estrogen receptor and HER2 levels.Conclusions: Our study shows that molecular profiling of low numbers of CTCs in a high background of leukocytes is feasible and shows promise for further studies on the clinical relevance of molecular characterization of CTCs.

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“…Among the parameters most significantly correlated with lymph node involvement are histological grade, tumor size and age (9,10). Furthermore, number and proportion of evaluated sentinel lymph node biopsies (SLNBs) have been correlated with metastases in the axillary lymph nodes (11)(12)(13)).…”

Section: Introductionmentioning

confidence: 99%

Analysis of molecular markers as predictive factors of lymph node involvement in breast carcinoma

Paula

Moraes²,

Canto³

et al. 2016

Oncology Letters

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Abstract. Nodal status is the most significant independent prognostic factor in breast cancer. Identification of molecular markers would allow stratification of patients who require surgical assessment of lymph nodes from the large numbers of patients for whom this surgical procedure is unnecessary, thus leading to a more accurate prognosis. However, up to now, the reported studies are preliminary and controversial, and although hundreds of markers have been assessed, few of them have been used in clinical practice for treatment or prognosis in breast cancer. The purpose of the present study was to determine whether protein phosphatase Mg2+/Mn2+ dependent 1D, β-1,3-N-acetylglucosaminyltransferase, neural precursor cell expressed, developmentally down-regulated 9, prohibitin, phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5), phosphatidylinositol-5-phosphate 4-kinase type IIα, TRF1-interacting ankyrin-related ADP-ribose polymerase 2, BCL2 associated agonist of cell death, G2 and S-phase expressed 1 and PAX interacting protein 1 genes, described as prognostic markers in breast cancer in a previous microarray study, are also predictors of lymph node involvement in breast carcinoma Reverse transcription-quantitative polymerase chain reaction analysis was performed on primary breast tumor tissues from women with negative lymph node involvement (n=27) compared with primary tumor tissues from women with positive lymph node involvement (n=23), and was also performed on primary tumors and paired lymph node metastases (n=11). For all genes analyzed, only the PIK3R5 gene exhibited differential expression in samples of primary tumors with positive lymph node involvement compared with primary tumors with negative lymph node involvement (P= 0.0347). These results demonstrate that the PIK3R5 gene may be considered predictive of lymph node involvement in breast carcinoma. Although the other genes evaluated in the present study have been previously characterized to be involved with the development of distant metastases, they did not have predictive potential.

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Molecular markers of breast axillary lymph node metastasis

Cited by 19 publications

References 181 publications

Collagen I fiber density increases in lymph node positive breast cancers: pilot study

Collagen I fiber density increases in lymph node positive breast cancers: pilot study

mRNA and microRNA Expression Profiles in Circulating Tumor Cells and Primary Tumors of Metastatic Breast Cancer Patients

Analysis of molecular markers as predictive factors of lymph node involvement in breast carcinoma

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