Variations in stromal signatures in breast and colorectal cancer metastases - PubMed (original) (raw)

Variations in stromal signatures in breast and colorectal cancer metastases

Jonathan A Webster et al. J Pathol. 2010 Oct.

Abstract

The tumour microenvironment (TME) plays an important role in tumour survival and growth, but little is known about the degree of preservation between different stromal response patterns found in primary tumours and their metastases. We have previously identified gene expression profiles for two distinct stromal signatures in breast carcinoma of fibroblast (aka DTF) and macrophage (aka CSF1) response and found them to be correlated with clinicopathological features, including outcome. In this study, we compare the DTF fibroblast and CSF1 macrophage stromal response patterns in primary breast and colorectal cancers to their matched lymph node metastases. In both breast and colorectal cancer, there was a significant positive correlation between the CSF1 macrophage signature in the primary tumours and the matched lymph node metastases, as assessed by immunohistochemical markers. No such correlation was observed for the DTF fibroblast signature. A similar result was seen in independent analysis of two published gene expression microarray datasets. The variations of these stromal reaction patterns from the primary to the metastasis shed light on the relationship between the neoplastic cells and the non-neoplastic cells in the TME. The preservation of the CSF1 macrophage response pattern in metastases lends support to targeting the CSF1 pathway in cancer.

Copyright 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Conflict of interest statement

Conflict of interest statement: The authors and the study sponsors have no conflict of interest in this work.

Figures

Figure 1

Figure 1

Representative images of the immunohistochemistry for selective markers. A) CTSL in a primary invasive ductal carcinoma of the breast. B) CTSL in a breast metastasis. C) CSPG2 in a primary invasive ductal carcinoma of the breast. D) CSPG2 in a breast metastasis. E) CD163 in a primary colonic adenocarcinoma. F) CD163 in a colonic adenocarcinoma metastasis. G) CD163 in a breast metastasis. H) SPARC in a primary colonic adenocarcinoma. I) SPARC in a colonic adenocarcinoma metastasis. J) SPARC in a breast metastasis.

Figure 2

Figure 2

Analysis of CSF1 macrophage response signature in 49 matched primary and regional lymph node metastatic breast cancer as measured by 4 immunohistochemical markers and displayed as a scatter plot of average marker score for each primary and regional lymph node metastatic breast cancer pair.

Figure 3

Figure 3

A) Gene expression profiling of 15 matched primary and regional lymph node metastatic breast cancers with the CSF1 macrophage response signature core gene set. The bar graph shows the sums of CSF1 macrophage response signature core for each matched pair, blue represents the primary and red represents the metastasis. B) Gene expression profiling of 8 matched primary and distant metastatic breast cancers. The bar graph shows the sums of CSF1 macrophage response signature core for each matched pair.

Figure 4

Figure 4

Results from the of CSF1 macrophage response signature in matched primary and metastatic colorectal cancer as a scatter plot of average marker score for each primary and regional lymph node metastatic breast cancer pair.

Figure 5

Figure 5

Analysis of DTF fibroblast stromal signature in matched primary and regional lymph node metastatic breast cancer for 5 DTF fibroblast response signature markers for a set of 49 primary and regional lymph node metastatic breast cancer pairings as a scatter plot of average marker score for each primary and regional lymph node metastatic breast cancer pair.

Figure 6

Figure 6

A) Gene expression profiling of 15 matched primary and regional lymph node metastatic breast cancers with the DTF fibroblast response signature core gene set. The bar graph shows the sums of DTF fibroblast response signature core for each matched pair, blue represents the primary and red represents the metastasis. B) Gene expression profiling of 8 matched primary and distant metastatic breast cancers. The bar graph shows the sums of DTF fibroblast response signature core for each matched pair.

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