The Journal of pathology
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The Journal of pathology · Oct 2008
Refinement of breast cancer classification by molecular characterization of histological special types.
Most invasive breast cancers are classified as invasive ductal carcinoma not otherwise specified (IDC NOS), whereas about 25% are defined as histological 'special types'. These special-type breast cancers are categorized into at least 17 discrete pathological entities; however, whether these also constitute discrete molecular entities remains to be determined. Current therapy decision-making is increasingly governed by the molecular classification of breast cancer (luminal, basal-like, HER2+). ⋯ When classified by expression profiling, IDC NOS and ILC contain all molecular breast cancer types (ie luminal, basal-like, HER2+), whereas histological special-type cancers, apart from apocrine carcinoma, are homogeneous and only belong to one molecular subtype. Our analysis also revealed that some special types associated with a good prognosis, such as medullary and adenoid cystic carcinomas, display a poor prognosis basal-like transcriptome, providing strong circumstantial evidence that basal-like cancers constitute a heterogeneous group. Taken together, our results imply that the correct classification of breast cancers of special histological type will allow a more accurate prognostication of breast cancer patients and facilitate the identification of optimal therapeutic strategies.
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The Journal of pathology · Oct 2008
Phagocyte-specific S100 proteins are released from affected mucosa and promote immune responses during inflammatory bowel disease.
Phagocyte-derived S100 proteins are endogenous activators of innate immune responses. S100A12 binds to the receptor for advanced glycation end-products, while complexes of S100A8/S100A9 (myeloid-related proteins, MRP8/14; calprotectin) are ligands of toll-like receptor 4. These S100 proteins can be detected in stool. ⋯ The direct release of phagocyte-derived S100 proteins from inflamed tissues may reflect secretion from infiltrating neutrophils (S100A12) and also monocytes or epithelial cells (MRP8/14). Via activation of pattern recognition receptors, these proteins promote inflammation in intestinal tissue. The enhanced mucosal release can explain the correlation of fecal markers with disease activity in IBD.
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The Journal of pathology · Sep 2008
Possible involvement of the M2 anti-inflammatory macrophage phenotype in growth of human gliomas.
Within tumours, many non-neoplastic cells such as fibroblasts, endothelial cells, and macrophages assist tumour growth by producing various growth factors and pro-angiogenic cytokines. Various tumour-derived molecules drive tumour-associated macrophages towards an anti-inflammatory phenotype (M2) and thus promoting tumour growth. Here we investigated microglia/macrophage differentiation in glioma tissues by means of immunostaining of paraffin-embedded glioma samples. ⋯ In addition, the proportion of M2 microglia/macrophages and M-CSF expression in tumour cells correlated well with proliferation of glioblastoma cells. These results suggest that tumour-derived M-CSF induces a shift of microglia/macrophages towards the M2 phenotype, which influences tumour growth. Evaluation of the proportion of M2 microglia/macrophages and M-CSF expression in tumour tissue would be useful for assessment of microglia/macrophage proliferative activity and the prognosis of patients with gliomas.
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The Journal of pathology · Dec 2007
Multiple genetic and epigenetic biomarkers for lung cancer detection in cytologically negative sputum and a nested case-control study for risk assessment.
The purpose of this study was to define a biomarker panel for detection of cancer cells in cytologically negative sputum and to evaluate the panel for assessment of lung cancer risk. We examined 19 genetic and epigenetic markers using a sensitive fluorescence-based method in cytologically negative sputum and in lung tumour tissues from 82 lung cancer patients. We also used these markers to test the sputum of 37 cancer-free individuals who were matched by age, sex, and smoking habit. ⋯ In the nested case-control study, six biomarkers showed significantly increased odds ratios ranging from 3.14 to 11.24. Our study defines a biomarker panel for detection of cancer cells in cytologically negative sputum and verifies its use for risk assessment of lung cancer. In combination with conventional diagnostic tools, this multiple genetic and epigenetic panel should improve the detection or risk assessment of lung cancer.
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The Journal of pathology · Jun 2007
The secretory leukocyte protease inhibitor (SLPI) suppresses cancer cell invasion but promotes blood-borne metastasis via an invasion-independent pathway.
An invasion-independent pathway has been proposed as a novel mechanism in blood-borne metastasis, where tumour cells enveloped by sinusoidal tumour vessels enter the circulation without vascular invasion. We previously identified the secretory leukocyte protease inhibitor (SLPI) as a candidate gene responsible for this pathway. In this study, the functional role of SLPI in metastatic dissemination was investigated. ⋯ In vivo angiogenesis assays also demonstrated that SLPI suppressed the migration of newly formed blood vessels. These results suggest that an anti-migratory effect of SLPI on tumour-associated endothelial cells may induce vascular remodelling to form a sinusoidal architecture, and consequently promote invasion-independent metastasis. This study provides a new model for metastasis, based on the mechanism regulated by anti-invasive factors, such as SLPI.