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No common denominator for breast cancer lymph node metastasis.

Weigelt B, Wessels LF, Bosma AJ, Glas AM, Nuyten DS, He YD, Dai H, Peterse JL, van't Veer LJ - Br. J. Cancer (2005)

Bottom Line: The axillary lymph node status is the most powerful prognostic factor for breast cancer patients to date.However, subtle differences in the expression of genes involved in extracellular-matrix organisation and growth factor signalling are detected in individual pairs of matching primary and metastatic tumours.Our data suggest that breast carcinomas do not use a shared gene set to accomplish lymph node metastasis.

View Article: PubMed Central - PubMed

Affiliation: Division of Experimental Therapy, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.

ABSTRACT
The axillary lymph node status is the most powerful prognostic factor for breast cancer patients to date. The molecular mechanisms that control lymph node metastasis, however, remain poorly understood. To define patterns of genes or gene regulatory pathways that drive breast cancer lymph node metastasis, we compared the gene expression profiles of 15 primary breast carcinomas and their matching lymph node metastases using microarrays. In general, primary breast carcinomas and lymph node metastases do not differ at the transcriptional level by a common subset of genes. No classifier or single gene discriminating the group of primary tumours from those of the lymph node metastases could be identified. Also, in a series of 295 breast tumours, no classifier predicting lymph node metastasis could be developed. However, subtle differences in the expression of genes involved in extracellular-matrix organisation and growth factor signalling are detected in individual pairs of matching primary and metastatic tumours. Surprisingly, however, different sets of these genes are either up- or downregulated in lymph node metastases. Our data suggest that breast carcinomas do not use a shared gene set to accomplish lymph node metastasis.

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Related in: MedlinePlus

(A) Unsupervised hierarchical clustering of 30 primary breast carcinomas and lymph node metastases from 15 patients, measured over 18 336 genes. The dendrogram has two large branches; the orange bar represents ER-α-negative and the green bar ER-α-positive tumours. Alignment of all matching pairs was established. (B) Permutation test of the WPBPSR. Blue:  hypothesis distribution. Distribution after randomisation of the labels of the primary and metastatic tumours, repeated 20 000 times (WPBPSR=1±0.05). The red line represents the WPBPSR of the 15 matching pairs (WPBPSR=0.45; P<0.0001). Prim=primary tumour; LNmeta=lymph node metastasis; Prim n, LNmeta n (n=1–17)=patient number primary tumour, patient number lymph node metastasis, respectively.
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fig1: (A) Unsupervised hierarchical clustering of 30 primary breast carcinomas and lymph node metastases from 15 patients, measured over 18 336 genes. The dendrogram has two large branches; the orange bar represents ER-α-negative and the green bar ER-α-positive tumours. Alignment of all matching pairs was established. (B) Permutation test of the WPBPSR. Blue: hypothesis distribution. Distribution after randomisation of the labels of the primary and metastatic tumours, repeated 20 000 times (WPBPSR=1±0.05). The red line represents the WPBPSR of the 15 matching pairs (WPBPSR=0.45; P<0.0001). Prim=primary tumour; LNmeta=lymph node metastasis; Prim n, LNmeta n (n=1–17)=patient number primary tumour, patient number lymph node metastasis, respectively.

Mentions: To further scrutinise our results, we examined the similarity between primary and matching metastatic tumours. Unsupervised hierarchical clustering, the grouping of tumours based on their similarity measured overall genes on the array, revealed that the gene expression profiles of primary breast and matching regional metastatic tumours are highly alike (Figure 1A). The division of the dendrogram into two branches is based on the highly dominant ER-α expression profile displayed by nine of the 15 tumours and matching metastases (Gruvberger et al, 2001; van 't Veer et al, 2002; Weigelt et al, 2003).


No common denominator for breast cancer lymph node metastasis.

Weigelt B, Wessels LF, Bosma AJ, Glas AM, Nuyten DS, He YD, Dai H, Peterse JL, van't Veer LJ - Br. J. Cancer (2005)

(A) Unsupervised hierarchical clustering of 30 primary breast carcinomas and lymph node metastases from 15 patients, measured over 18 336 genes. The dendrogram has two large branches; the orange bar represents ER-α-negative and the green bar ER-α-positive tumours. Alignment of all matching pairs was established. (B) Permutation test of the WPBPSR. Blue:  hypothesis distribution. Distribution after randomisation of the labels of the primary and metastatic tumours, repeated 20 000 times (WPBPSR=1±0.05). The red line represents the WPBPSR of the 15 matching pairs (WPBPSR=0.45; P<0.0001). Prim=primary tumour; LNmeta=lymph node metastasis; Prim n, LNmeta n (n=1–17)=patient number primary tumour, patient number lymph node metastasis, respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361648&req=5

fig1: (A) Unsupervised hierarchical clustering of 30 primary breast carcinomas and lymph node metastases from 15 patients, measured over 18 336 genes. The dendrogram has two large branches; the orange bar represents ER-α-negative and the green bar ER-α-positive tumours. Alignment of all matching pairs was established. (B) Permutation test of the WPBPSR. Blue: hypothesis distribution. Distribution after randomisation of the labels of the primary and metastatic tumours, repeated 20 000 times (WPBPSR=1±0.05). The red line represents the WPBPSR of the 15 matching pairs (WPBPSR=0.45; P<0.0001). Prim=primary tumour; LNmeta=lymph node metastasis; Prim n, LNmeta n (n=1–17)=patient number primary tumour, patient number lymph node metastasis, respectively.
Mentions: To further scrutinise our results, we examined the similarity between primary and matching metastatic tumours. Unsupervised hierarchical clustering, the grouping of tumours based on their similarity measured overall genes on the array, revealed that the gene expression profiles of primary breast and matching regional metastatic tumours are highly alike (Figure 1A). The division of the dendrogram into two branches is based on the highly dominant ER-α expression profile displayed by nine of the 15 tumours and matching metastases (Gruvberger et al, 2001; van 't Veer et al, 2002; Weigelt et al, 2003).

Bottom Line: The axillary lymph node status is the most powerful prognostic factor for breast cancer patients to date.However, subtle differences in the expression of genes involved in extracellular-matrix organisation and growth factor signalling are detected in individual pairs of matching primary and metastatic tumours.Our data suggest that breast carcinomas do not use a shared gene set to accomplish lymph node metastasis.

View Article: PubMed Central - PubMed

Affiliation: Division of Experimental Therapy, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.

ABSTRACT
The axillary lymph node status is the most powerful prognostic factor for breast cancer patients to date. The molecular mechanisms that control lymph node metastasis, however, remain poorly understood. To define patterns of genes or gene regulatory pathways that drive breast cancer lymph node metastasis, we compared the gene expression profiles of 15 primary breast carcinomas and their matching lymph node metastases using microarrays. In general, primary breast carcinomas and lymph node metastases do not differ at the transcriptional level by a common subset of genes. No classifier or single gene discriminating the group of primary tumours from those of the lymph node metastases could be identified. Also, in a series of 295 breast tumours, no classifier predicting lymph node metastasis could be developed. However, subtle differences in the expression of genes involved in extracellular-matrix organisation and growth factor signalling are detected in individual pairs of matching primary and metastatic tumours. Surprisingly, however, different sets of these genes are either up- or downregulated in lymph node metastases. Our data suggest that breast carcinomas do not use a shared gene set to accomplish lymph node metastasis.

Show MeSH
Related in: MedlinePlus