Introduction Stromal cell-derived factor (SDF)-1 (CXC chemokine ligand-12) is a member of the CXC subfamily of chemokines, which, through its cognate receptor (CXC chemokine receptor [CXCR]4), plays an important role in chemotaxis of cancer cells and in tumour metastasis. We conducted the present study to evaluate the effect of SDF-1 on the invasiveness and migration of breast cancer cells, and we analyzed the expression of SDF-1 and its relation to clinicopathological features and clinical outcomes in human breast cancer.

Introduction: To investigate the expression of EPLIN-α, epithelial protein lost in neoplasm, in human breast cancer tissues/cells and investigate the cellular impact of EPLIN-α on breast cancer cells.

The CCN family members cysteine-rich 61 (Cyr61/CCN1), connective tissue growth factor (CTGF/ CCN2) and nephroblastoma over-expressed (Nov/CCN3) play diverse roles in cells, are known to regulate cell growth, adhesion, matrix production and migration and are involved in endocrineregulated pathways in various cell types. The role of these molecules in cancer remains controversial. In a cohort of 122 human breast tumours (together with 32 normal breast tissues) we have analysed the expression of all three CCN members at the mRNA and protein levels. Significantly higher levels of Cyr61 ðP ¼ 0:02Þ, but low levels of CTGF and Nov, were seen in tumour tissues compared with normal tissues. Significantly raised levels of Cyr61 were associated with poor prognosis ðP ¼ 0:02Þ, nodal involvement ðP ¼ 0:03Þ and metastatic disease ðP ¼ 0:016Þ. Patients who died of breast cancer also had high levels of Cyr61. In contrast, CTGF in patients with poor prognosis ðP ¼ 0:021Þ, metastasis ðP ¼ 0:012Þ, local recurrence ðP ¼ 0:0024Þ and mortality ðP ¼ 0:0072Þ had markedly reduced levels. Similar to CTGF, low levels of Nov were also seen in patients with poor prognosis and mortality and with significantly decreased survival (P ¼ 0:033 and P ¼ 0:0146, respectively). This result was fully supported by immunohistochemical analysis of frozen sectioned tissues. While fibroblasts and endothelial cells generally expressed good levels of all three CCN proteins, highly invasive MDA MB 231 cells expressed lower levels of CTGF and Nov, but higher levels of Cyr61, than the less invasive MCF-7. It is concluded that members of the CCN family are differentially expressed and may play important but contrasting roles in the progressive nature of human breast cancer. While Cyr61 appears to act as a factor stimulating aggressiveness, CTGF and Nov may act as tumour suppressors.

We undertook a retrospective pathological study of 118 skin resection specimens from 101 patients with hidradenitis suppurativa. Follicular occlusion was identified in all the specimens, regardless of disease duration (1 month to 18 years), but was not noted in the axillary and inguinal skin of controls. We therefore regard follicular occlusion as an early and important feature in the pathogenesis of the disease. The presence of apoeccrine glands in axillary skin provided an in vivo model to directly observe the effects of follicular occlusion on follicle inflammation and apocrine gland destruction. In the majority of cases, active folliculitis was associated with apocrinitis and apocrine destruction, whereas apoeccrine glands, which drain directly on to the epidermal surface, appeared intact and non-inflamed. These observations provide direct evidence in an in vivo model that follicular occlusion by keratinous material, with subsequent active folliculitis and secondary destruction of the skin adnexae and subcutis, occur as an integral step in the pathogenesis of hidradenitis suppurativa.

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Peroxisome-proliferator activated receptor-gamma (PPAR␥) belongs to a family of nuclear receptors and acts as receptor for peroxisome-proliferators, steroids, retinoic acids, and polyunsaturated fatty acids. Our study examined the transcript levels of peroxisome-proliferator activated receptorgamma (PPAR␥) and its co-activator (PGC-1) in a cohort of patients with breast cancer. An invasive breast cancer cell, MDA MB 231 exhibited lower level of expression of PPAR␥, compared to non-invasive MCF-7. Breast cancer tissues (n ‫؍‬ 120) exhibited a lower level of PPAR␥ mRNA compared to normal tissues (n ‫؍‬ 25, p ‫؍‬ 0.05). No difference, however, was seen with PGC-1. Although the levels of PPAR␥ and PGC-1 did not correlate with nodal involvement and grade, significantly lower levels of PPAR␥ were seen in TNM3 and TNM4 tumors and from patients with local recurrence and those who died of breast cancer. Lowest level of PGC-1 was also seen in TNM3 and TNM4 tumors and patients who died of breast cancer. We conclude that there is aberrant expression of PPAR␥ and its co-activator, PGC-1, in human breast cancer and low levels of these molecules in cancer tissues are associated with poor clinical outcomes. Peroxisome proliferator activator receptor-gamma (PPAR␥) belongs to a nuclear hormone receptor superfamily that regulates gene expression. 1-3 PPAR␥ contain DNA, lipid and A/B binding domains that recognize DNA response elements in the promoters of their target genes and interact with lipid ligands 4 and prostaglandins (PG J2). 5,6 Ligands for PPAR␥ such as troglitazone, BRL 49653, 15S-hydroxyeicosatetraenoic acid , and 15-deoxy-Delta 12,14-prostaglandin J2 have been shown to inhibit the growth of tumors and induce apoptosis of cancer cells, 7-10 and inhibit colon tumorigenesis in animal models. 11-14 PPAR␥ forms a complex with the PPAR␥ coactivators (PGC-1 and PGC-2) 21,22 and, together with other transcription factors SRC-1 and the CREB binding protein, 23 regulates gene expression, including cyclin regulator p27kip1, cMET protooncogene, and E-cadherin. The inhibition of cell growth by PPAR␥ agonists appears to be via multiple ways, including the inhibition of cyclin D1 15 and increase the level of cell cycle inhibitor P27 kip1 . 16 The proliferation of cancer cells that express PPAR␥ can be inhibited by its ligands and, interestingly, that the effect can be further enhanced by 9-cis retinoic acid, a ligand of RXR alpha. 17 PPAR␥ agonists can also reduce the growth and progressive activities of prostate cancer cells 18,19 and inhibit transcription of genes that are involved in tumor progression, such as the HGF receptor, cMET. 20 Abnormalities in PPAR family members have been implicated in tumorigenesis in animal models and in human cancers. PPAR␣ has been shown to be overexpressed in human prostate cancer. 24,25 Mutation of PPAR␥ has also been reported on colorectal cancer. PPAR␥ can be upregulated by agents such as butyrate in cancer cells. 26 We and others have shown that polyunsaturated fatty acids, such as gamma linol...

The indiscriminate use of SLNB in patients with DCIS seems excessive. Our study suggests that patients with a mass on clinical examination or mammogram have an increased risk of invasive disease at the time of definitive operative procedure and should undergo SLNB at the initial procedure. In addition, SLNB should be performed in patients undergoing mastectomy because mastectomy precludes SLNB if invasive disease is subsequently discovered.