Molecular signatures of lymph node status by intrinsic subtype: gene expression analysis of primary breast tumors from patients with and without metastatic lymph nodes

In our previous study, calcitriol and its analogs PRI-2191 and PRI-2205 stimulated 4T1 mouse mammary gland cancer metastasis. Therefore, we aimed to analyze the inflammatory response in 4T1-bearing mice treated with these compounds. Gene expression analysis of the splenocytes and regional lymph nodes demonstrated prevalence of the T helper lymphocytes (Th2) response with an increased activity of regulatory T (Treg) lymphocytes in mice treated with these compounds. We also observed an increased number of mature granulocytes and B lymphocytes and a decreased number of TCD4+, TCD4+CD25+, and TCD8+, as well as natural killer (NK) CD335+, cells in the blood of mice treated with calcitriol and its analogs. Among the splenocytes, we observed a significant decrease in NK CD335+ cells and an increase in TCD8+ cells. Calcitriol and its analogs decreased the levels of interleukin (IL)-1β and IL-10 and increased the level of interferon gamma (IFN-γ) in the plasma. In the tumor tissue, they caused an increase in the level of IL-10. Gene expression analysis of lung tissue demonstrated an increased level of osteopontin (Spp1) and transforming growth factor β (TGF-β) mRNA. The expression of Spp1 was also elevated in lymph nodes. Calcitriol and its analogs caused prevalence of tumor-conducive changes in the immune system of 4T1 tumor-bearing mice, despite the induction of some tumor-disadvantageous effects.

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Sodium-iodide symporter (NIS) gene expression in lymph-node metastases of papillary thyroid carcinomas

Acta Endocrinologica ◽

10.1530/eje.0.1430623 ◽

2000 ◽

pp. 623-627 ◽

Cited By ~ 45

Author(s):

F Arturi ◽

D Russo ◽

D Giuffrida ◽

M Schlumberger ◽

S Filetti

Keyword(s):

Gene Expression ◽

Lymph Node ◽

Lymph Nodes ◽

Papillary Thyroid ◽

Iodide Uptake ◽

Metastatic Lymph Nodes ◽

Thyroid Carcinomas ◽

Metastatic Lymph ◽

Nis Gene ◽

Total Body

OBJECTIVE: To investigate the molecular mechanisms underlying the influence of alteration of iodine trapping on the prognosis of metastatic papillary thyroid carcinomas, focusing on the expression of the Na+/I(-) symporter (NIS). DESIGN: We evaluated the expression of the NIS gene in a series of 11 enlarged neck lymph-node metastases of papillary thyroid carcinomas, including four patients in whom an enlarged lymph node represented the first sign of the tumoral disease. Nine lymph nodes, either reactive or metastatic for non-thyroid tumors, were also investigated. METHODS: Expression of the NIS gene was evaluated by RT-PCR in material obtained by fine-needle aspiration biopsy. RESULTS: The NIS gene was expressed in eight (73%) of 11 differentiated thyroid cancer metastatic lymph nodes examined. Five of these metastatic lymph nodes were positive at the post-treatment total-body iodine-131 scan; in the other three, the total-body scan showed no uptake in the metastatic tissues, indicating an alteration downstream to the NIS mRNA synthesis causing the loss of iodide uptake. As expected, when the NIS mRNA expression was absent, total-body (131)I scan showed no uptake in the metastatic lymph nodes. CONCLUSIONS: Our study demonstrates that NIS gene expression may be absent in metastatic differentiated thyroid carcinomas and that different mechanisms, other than loss of NIS transcription, may also be involved in the loss of iodide uptake in metastatic thyroid cells. Study of NIS gene expression in the metastatic lymph nodes, therefore, may provide useful information in the management of patients with thyroid carcinoma.

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Differential Gene Expression in Primary Breast Tumors Associated with Lymph Node Metastasis

International Journal of Breast Cancer ◽

10.4061/2011/142763 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 10

Author(s):

Rachel E. Ellsworth ◽

Lori A. Field ◽

Brad Love ◽

Jennifer L. Kane ◽

Jeffrey A. Hooke ◽

...

Keyword(s):

Gene Expression ◽

Lymph Node ◽

Breast Tumors ◽

Host Susceptibility ◽

Prognostic Indicators ◽

Lymph Node Status ◽

Primary Tumors ◽

Node Negative ◽

Node Positive ◽

Node Status

Lymph node status remains one of the most useful prognostic indicators in breast cancer; however, current methods to assess nodal status disrupt the lymphatic system and may lead to secondary complications. Identification of molecular signatures discriminating lymph node-positive from lymph node-negative primary tumors would allow for stratification of patients requiring surgical assesment of lymph nodes. Primary breast tumors from women with negative () and positive () lymph node status matched for possible confounding factors were subjected to laser microdissection and gene expression data generated. Although ANOVA analysis (, fold-change >1.5) revealed 13 differentially expressed genes, hierarchical clustering classified 90% of node-negative but only 66% of node-positive tumors correctly. The inability to derive molecular profiles of metastasis in primary tumors may reflect tumor heterogeneity, paucity of cells within the primary tumor with metastatic potential, influence of the microenvironment, or inherited host susceptibility to metastasis.

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Lymph node status assessment for gastric carcinoma: Is the number of metastatic lymph nodes really practical as a parameter for N categories in the TNM classification?

Journal of Surgical Oncology ◽

10.1002/(sici)1096-9098(199809)69:1<15::aid-jso4>3.0.co;2-n ◽

1998 ◽

Vol 69 (1) ◽

pp. 15-20 ◽

Cited By ~ 40

Author(s):

Yasuhiro Kodera ◽

Yoshitaka Yamamura ◽

Yasuhiro Shimizu ◽

Akihito Torii ◽

Takashi Hirai ◽

...

Keyword(s):

Lymph Node ◽

Gastric Carcinoma ◽

Lymph Nodes ◽

Tnm Classification ◽

Lymph Node Status ◽

Metastatic Lymph Nodes ◽

Metastatic Lymph ◽

Node Status ◽

Status Assessment

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Gene Expression Analysis Identifies a Signature Related to Lymph Node Metastasis of T1/2 Tumors Compared to Controls

Journal of Oral and Maxillofacial Surgery ◽

10.1016/j.joms.2013.06.060 ◽

2013 ◽

Vol 71 (9) ◽

pp. e34-e35

Author(s):

K. Patel ◽

D. Kademani ◽

L. Zhang

Keyword(s):

Gene Expression ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Expression Analysis ◽

Gene Expression Analysis ◽

Node Metastasis

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Identification of proteins promoting development of metastatic breast tumors

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.1041 ◽

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.

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