Identification of proteins promoting development of metastatic breast tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1041-1041
Author(s):  
E. Seeley ◽  
R. E. Ellsworth ◽  
D. Ellsworth ◽  
M. Sanders ◽  
J. A. Hooke ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Metastatic Disease ◽  
Metastatic Breast ◽  
Breast Tumors ◽  
Lymph Node Status ◽  
Thymosin Β4 ◽  
Treatment Regimens ◽  
Specific Subset

1041 Background: Primary breast tumors are constantly shedding tumor cells into the circulatory and lymphatic systems. Although detection of occult tumor cells is a risk factor for recurrence and progression, tumor cells remain detectable years after initial diagnosis in patients without clinical or histological detection of metastasis. Thus the question remains as to why some women with circulating tumor cells develop metastatic breast cancer while others do not. Methods: Negative lymph nodes from women with node negative (n=22) and node positive disease (n=36) were obtained from patients enrolled in the Clinical Breast Care Project. Negative lymph node status was confirmed by IHC analysis. Frozen tissues were sectioned and mounted on gold coated MALDI target plates for protein expression profiling. Hematoxylin and eosin (H&E) stained slides were prepared from serial sections for histological characterization. MALDI matrix was deposited as individual spots on the tissue sections in a histology directed manner to assay specific areas and tissue types of interest. Mass spectral data were then acquired from multiple sites across each tissue section. Results: 131 features were observed in negative nodes from patients without metastatic disease and 129 in negative nodes from patients with lymph node metastases. While the majority of features detected were similar between the two groups, 8.5% were differentially expressed. Two of the features which were expressed at significantly higher levels in nodes from patients with metastatic disease have been putatively identified as thymosin β4 and thymosin β10. Conclusions: Thymosin β4 and 10 have been associated with disease progression and metastatic capacity in a number of tumor types. The overexpression of these proteins in tumor-negative nodes from patients with metastatic disease in other regional nodes suggests lymph nodes do not play a passive role in metastasis, rather, expression of a specific subset of proteins creates an hospitable environment to facilitate colonization. These markers of metastasis may permit molecular discrimination of those patients with indolent disease from those at risk for metastasis and will thus allow for the design of customized treatment regimens to more effectively treat, or prevent, metastatic spread. No significant financial relationships to disclose.

scholarly journals SP140L is differentially expressed in metastasis to lymph nodes in human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Human Breast Cancer ◽  
Metastatic Breast ◽  
Human Breast ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the brain and the breast resides the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in human breast cancer. We found that the SP140 nuclear body protein like, encoded by SP140L, was among the genes whose expression was most different in the lymph nodes metastases of patients with metastatic breast cancer as compared to primary tumors of the breast (4). SP140L was also differentially expressed in the tumor cells of patients with triple negative breast cancer (5). SP140L mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Importantly, expression of SP140L in primary tumors was significantly correlated with patient overall survival, in lymph node positive patients but not in lymph node negative patients. Modulation of SP140L expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph node and to the brain in humans with metastatic breast cancer.

scholarly journals CCDC155 is differentially expressed in metastasis to lymph nodes in human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Human Breast Cancer ◽  
Metastatic Breast ◽  
Human Breast ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the brain and the breast resides the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in human breast cancer. We found that the coiled-coil domain containing 155, encoded by CCDC155, was among the genes whose expression was most different in the lymph nodes metastases of patients with metastatic breast cancer as compared to primary tumors of the breast (4). CCDC155 was also differentially expressed in the tumor cells of patients with triple negative breast cancer (5). CCDC155 mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Importantly, expression of CCDC155 in primary tumors was significantly correlated with patient recurrence-free survival, in lymph node positive patients but in lymph node negative patients. Modulation of CCDC155 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph node and to the brain in humans with metastatic breast cancer.

scholarly journals ZNF367 is differentially expressed in metastasis to lymph nodes in human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Human Breast Cancer ◽  
Metastatic Breast ◽  
Human Breast ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the brain and the breast resides the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in human breast cancer. We found that the zinc finger protein 367, encoded by ZNF367, was among the genes whose expression was most different in the lymph nodes metastases of patients with metastatic breast cancer as compared to primary tumors of the breast4. ZNF367 was also differentially expressed in the tumor cells of patients with triple negative breast cancer5. ZNF367 mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Importantly, expression of ZNF367 in primary tumors was significantly correlated with patient distant metastasis-free survival, in lymph node negative but not in lymph node positive breast cancer. Modulation of ZNF367 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

scholarly journals TSNAXIP1 is differentially expressed in metastasis to lymph nodes in human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Human Breast Cancer ◽  
Metastatic Breast ◽  
Human Breast ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the brain and the breast resides the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in human breast cancer. We found that translin associated factor X interacting protein 1, encoded by TSNAXIP1, was among the genes whose expression was most different in the lymph nodes metastases of patients with metastatic breast cancer as compared to primary tumors of the breast4. TSNAXIP1 was also differentially expressed in the tumor cells of patients with triple negative breast cancer5. TSNAXIP1 mRNA was present at decreased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Importantly, expression of TSNAXIP1 in primary tumors was significantly correlated with patient overall survival, in lymph node positive patients but in lymph node negative patients. Modulation of TSNAXIP1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph node and to the brain in humans with metastatic breast cancer.

scholarly journals Artificial Intelligence–Based Breast Cancer Nodal Metastasis Detection: Insights Into the Black Box for Pathologists

2018 ◽  
Vol 143 (7) ◽  
pp. 859-868 ◽  
Author(s):  
Yun Liu ◽  
Timo Kohlberger ◽  
Mohammad Norouzi ◽  
George E. Dahl ◽  
Jenny L. Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Artificial Intelligence ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Metastatic Breast ◽  
Nodal Metastasis ◽  
Clinical Implementation ◽  
Artificial Intelligence Algorithm ◽  
Tumor Level

Context.— Nodal metastasis of a primary tumor influences therapy decisions for a variety of cancers. Histologic identification of tumor cells in lymph nodes can be laborious and error-prone, especially for small tumor foci. Objective.— To evaluate the application and clinical implementation of a state-of-the-art deep learning–based artificial intelligence algorithm (LYmph Node Assistant or LYNA) for detection of metastatic breast cancer in sentinel lymph node biopsies. Design.— Whole slide images were obtained from hematoxylin-eosin–stained lymph nodes from 399 patients (publicly available Camelyon16 challenge dataset). LYNA was developed by using 270 slides and evaluated on the remaining 129 slides. We compared the findings to those obtained from an independent laboratory (108 slides from 20 patients/86 blocks) using a different scanner to measure reproducibility. Results.— LYNA achieved a slide-level area under the receiver operating characteristic (AUC) of 99% and a tumor-level sensitivity of 91% at 1 false positive per patient on the Camelyon16 evaluation dataset. We also identified 2 “normal” slides that contained micrometastases. When applied to our second dataset, LYNA achieved an AUC of 99.6%. LYNA was not affected by common histology artifacts such as overfixation, poor staining, and air bubbles. Conclusions.— Artificial intelligence algorithms can exhaustively evaluate every tissue patch on a slide, achieving higher tumor-level sensitivity than, and comparable slide-level performance to, pathologists. These techniques may improve the pathologist's productivity and reduce the number of false negatives associated with morphologic detection of tumor cells. We provide a framework to aid practicing pathologists in assessing such algorithms for adoption into their workflow (akin to how a pathologist assesses immunohistochemistry results).

scholarly journals The presence of metastases in regional lymph nodes is associated with tumor size and depth of invasion in sporadic gastric adenocarcinoma

2014 ◽  
Vol 27 (1) ◽  
pp. 18-21 ◽  
Author(s):  
Eduardo CAMBRUZZI ◽  
Andreza Mariane de AZEREDO ◽  
Ardala KRONHART ◽  
Katia Martins FOLTZ ◽  
Cláudio Galeano ZETTLER ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Gastric Adenocarcinoma ◽  
Tumor Size ◽  
Perineural Invasion ◽  
Histological Grade ◽  
Lymph Node Status ◽  
Depth Of Invasion ◽  
Tumor Spread ◽  
Signet Ring

Background: Gastric adenocarcinoma is more often found in men over 50 years in the form of an antral lesion. The tumor has heterogeneous histopathologic features and a poor prognosis (median survival of 15% in five years). Aim: To estimate the relationship between the presence of nodal metastasis and other prognostic factors in sporadic gastric adenocarcinoma. Method: Were evaluated 164 consecutive cases of gastric adenocarcinoma previously undergone gastrectomy (partial or total), without clinical evidence of distant metastasis, and determined the following variables: topography of the lesion, tumor size, Borrmann macroscopic configuration, histological grade, early or advanced lesions, Lauren histological subtype, presence of signet ring cell, degree of invasion, perigastric lymph node status, angiolymphatic/perineural invasion, and staging. Results: Were found 21 early lesions (12.8%) and 143 advanced lesions (87.2%), with a predominance of lesions classified as T3 (n=99/60, 4%) and N1 (n=62/37, 8%). The nodal status was associated with depth of invasion (p<0.001) and tumor size (p<0.001). The staging was related to age (p=0.048), histological grade (p=0.003), and presence of signet ring cells (p = 0.007), angiolymphatic invasion (p = 0.001), and perineural invasion (p=0.003). Conclusion: In gastric cancer, lymph node involvement, tumor size and depth of invasion are histopathological data associated with the pattern of growth/tumor spread, suggesting that a wide dissection of perigastric lymph nodes is a fundamental step in the surgical treatment of these patients.

scholarly journals Circulating tumor cells: silent predictors of metastasis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1445 ◽  
Author(s):  
LanLan Zhou ◽  
David T. Dicker ◽  
Elizabeth Matthew ◽  
Wafik S. El-Deiry ◽  
R. Katherine Alpaugh
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Disease ◽  
Metastatic Breast ◽  
Prognostic Indicator ◽  
Disease Recurrence ◽  
Curative Intent ◽  
Early Detection Of Disease ◽  
Mere Presence ◽  
Intent To Treat

Circulating tumor cells (CTCs) were added to the arsenal of clinical testing in 2004 for three cancer types: metastatic breast, prostate, and colorectal cancer. CTCs were found to be an independent prognostic indicator of survival for these three diseases. Multiple enrichment/isolation strategies have been developed and numerous assay applications have been performed using both single and pooled captured/enriched CTCs. We have reviewed the isolation techniques and touched on many analyses. The true utility of a CTC is that it acts as a “silent” predictor of metastatic disease. The mere presence of a single CTC is an indication that disease has spread from the primary site. Comments and suggestions have been set forth for CTCs and cell-free DNA to be used as a screening panel for the early detection of disease recurrence and metastatic spread, providing the opportunity for early intervention with curative intent to treat metastatic disease.

scholarly journals COL16A1 is differentially expressed in lymph node metastasis in human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Lymph Node Metastases ◽  
Metastatic Breast ◽  
Lymphoid Organ ◽  
Primary Tumors ◽  
Node Metastases ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that collagen type XVI alpha 1 chain, COL16A1, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. COL16A1 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of COL16A1 in primary tumors of the breast was correlated with patient overall survival, in lymph node negative patients but not in lymph node positive patients. Modulation of COL16A1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

scholarly journals COL6A1 is differentially expressed in lymph node metastasis in human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Lymph Node Metastases ◽  
Metastatic Breast ◽  
Lymphoid Organ ◽  
Primary Tumors ◽  
Node Metastases ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that collagen type VI alpha 1 chain, COL6A1, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. COL6A1 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of COL6A1 in primary tumors of the breast was correlated with patient post-progression survival, in lymph node negative patients but not in lymph node positive patients. Modulation of COL6A1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

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