Purpose: We characterized interleukin-8 (IL-8) and IL-8 receptor expression (CXCR1 and CXCR2) in prostate cancer to address their significance to this disease. Experimental Design: Immunohistochemistry was conducted on 40 cases of human prostate biopsy containing histologically normal and neoplastic tissue, excised from patients with locally confined or invasive androgen-dependent prostate cancer, and 10 cases of transurethral resection of the prostate material from patients with androgen-independent disease. Results: Weak to moderate IL-8 expression was strictly localized to the apical membrane of normal prostate epithelium. In contrast, membranous expression of IL-8, CXCR1, and CXCR2 was nonapical in cancer cells of Gleason pattern 3 and 4, whereas circumferential expression was present in Gleason pattern 5 and androgen-independent prostate cancer. Each of IL-8, CXCR1, and CXCR2 were also increasingly localized to the cytoplasm of cancer cells in correlation with advancing stage of disease. Cytoplasmic expression (but not apical membrane expression) of IL-8 in Gleason pattern 3 and 4 cancer correlated with Ki-67 expression (R = 0.79; P < 0.001), cyclin D1expression (R = 0.79; P < 0.001), and microvessel density (R = 0.81; P < 0.001). In vitro studies on androgen-independent PC3 cells confirmed the mitogenic activity of IL-8, increasing the rate of cell proliferation through activation of both CXCR1and CXCR2 receptors. Conclusions: We propose that the concurrent increase in IL-8 and IL-8 receptor expression in human prostate cancer induces autocrine signaling that may be functionally significant in initiating and promoting the progression of prostate cancer by underpinning cell proliferation and angiogenesis.

BackgroundThere is a growing body of evidence that immune response plays a large role in cancer outcome. The neutrophil to lymphocyte ratio (NLR) has been used as a simple parameter of systemic inflammation in several tumors. The purpose was to investigate the association between pre-treatment NLR, disease-free survival and overall survival in patients with early triple negative breast cancer (TNBC).MethodsWe reviewed the records of patients with stage I-III TNBC at our Institution from 2006 to 2012. The association between pre-treatment NLR and survival was analyzed. The difference among variables was calculated by chi-square test. DFS and OS were estimated using Kaplan-Meier method. Cox analysis was performed to analyze clinical parameters for their prognostic relevance.ResultsA total of 90 patients were eligible. There was no significant correlation among pre-treatment NLR and various clinical pathological factors. Patients with NLR higher than 3 showed significantly lower DFS (p = 0.002) and OS (p = 0.009) than patients with NLR equal or lower than 3. The Cox proportional multivariate hazard model revealed that higher pre-treatment NLR was independently correlated with poor DFS and OS, with hazard ratio 5.15 (95% confidence interval [CI] 1.11-23.88, p = 0.03) and 6.16 (95% CI 1.54-24.66, p = 0.01) respectively.ConclusionOur study suggests that pre-treatment NLR may be associated with DFS and OS patients with early TNBC. Further validation and a feasibility study are required before it can be considered for clinical use.

In this prospective study, we determined HER-2 status in primary breast invasive carcinomas and in the paired lymph node metastases (synchronous and metachronous), local recurrence and metachronous distant metastases, to verify the percentage of discordant cases. HercepTest TM and Fluorescence in situ hybridization (FISH) were used to determine HER-2 status on 119 cases of primary infiltrating breast carcinoma and paired metastases (45 cases with synchronous lymph node metastases, 9 cases with metachronous lymph node metastases, 30 cases with local recurrence, and 35 cases with metachronous distant metastases). A therapeutically significant HER-2 status discordance was demonstrated between primary carcinoma and synchronous lymph node metastases (6.7%), local recurrence (13.3%) and metachronous distant metastases (28.6%). In the first comparison, there was a normal HER-2 status in primary tumours and HER-2 amplification in paired metastases, in the second the opposite phenomenon was present, and both types of discordance were evident in the third comparison. Considering the cases of local recurrences and metachronous distant metastases all together, 14 out of 65 cases (21.5%) showed a therapeutically significant discordance of HER-2 status between the primary tumour and the paired metachronous recurrence or metastasis (p < 0.001), the 15.4% of cases showing normal HER-2 status in the primary tumour and HER-2 amplification in the neoplastic relapse. For the treatment of metastatic patients, the evaluation of HER-2 status should be performed in neoplastic tissue from metastatic site, whenever possible. This procedure could be also suggested in the patients that are metastatic at the time of diagnosis. ' 2007 Wiley-Liss, Inc.Key words: breast carcinoma; FISH; HER-2/neu; HercepTest TM ; metastasis The HER-2 proto-oncogene is located on chromosome 17q21 and encodes a transmembrane tyrosine kinase protein, which belongs to the epithelial growth factor receptors (EGFRs) family. Overexpression of the receptor or amplification of the HER-2 gene has been identified in 15-25% of invasive breast carcinomas and is very important both for the prognosis, 1 and for the therapy. 2,3 Trastuzumab is a humanized monoclonal antibody, which is used in the therapy of invasive breast carcinomas overexpressing HER-2 protein and/or showing HER-2 gene amplification. Trastuzumab treatment, in combination with chemotherapy, has given very good results, in terms of disease free survival and overall survival times, in patients with metastatic breast cancer 2 ; moreover, the results of recent trials on the efficacy of the drug in an adjuvant regimen have showed excellent results in terms of drastic reduction of the precocious relapses, when combined with chemotherapy. 4,5 Immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH) are the techniques recommended for HER-2 determination, according to the algorithm showed in Figure 1. Chromogenic in situ hybridization (CISH) has furnished promising results but is not yet considered an...

Vascular endothelial growth factor (VEGF) is a glycoprotein that has the capability to increase vascular proliferation and permeability. VEGF has been found to be expressed in several different types of tumors, and it may contribute to the progression of malignant tumors. Immunostaining for VEGF and factor VIII was performed in normal healthy pulps and in irreversible pulpitis. In both cases the vessels were always positive for VEGF. Our immunohistochemical data show that the expression of VEGF was strongly positive in the inflammatory infiltrate in irreversible pulpitis. VEGF expression in the stromal cells in healthy pulps ranged from 20 to 100% (with a mean of 68.82), and in irreversible pulpitis ranged from 0 to 100% (with a mean of 62.35%); this difference was statistically significant (p = 0.05). This down-regulation in the stromal cells in irreversible pulpitis could be due to the presence, in a low compliance system such as the dental pulp, of inflammatory infiltrate. VEGF is probably a factor implicated in the etiology and progression of pulpitis. The microvessel density in healthy pulps was 90.00 +/- 27.5, while, in irreversible pulpitis, it was 56.68 +/- 21.15. This difference was statistically significant (p = 0.001). The decrease in microvessel density in irreversible pulpitis could be related to failing vascular function and blood flow decrease.

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BACKGROUND Recent studies have demonstrated that angiogenesis is a potent prognostic indicator for patients with prostate cancer (PCa) and have pointed out that the evaluation of vascular endothelial growth factor (VEGF) is useful in assessing the angiogenic phenotype in PCa. The aim of the study was to investigate immunohistochemically the expression of VEGF and its correlation with the pattern of capillary architecture in prostate cancer and high‐grade prostatic intraepithelial neoplasia (PIN), in untreated and androgen‐ablated patients. METHODS Forty‐five patients who underwent radical prostatectomy (RP) for localized prostate carcinoma were recruited for this study. The study population included two groups: 35 patients who did not receive chemo‐, hormone, or radiation therapy before surgery, and 10 patients who were under complete androgen blockade (CAB) for 3 months at time of surgery. VEGF was examined by immunohistochemistry, and its tissue expression was compared with the pattern of capillary architecture evaluated by immunostaining the endothelial antigen CD34. The relationship of VEGF expression to chromogranin A‐positive (e.g., neuroendocrine) cells was investigated. RESULTS In normal tissue, the intensity of the VEGF immunoreactivity in the cytoplasm of secretory cells ranged from negative to low. Very few basal cells stained for VEGF. All prostate cancer specimens stained positively, the intensity of the immunoreaction ranging from low to strong and being correlated with the Gleason score. Strongly positive VEGF immunoreactivity was detected in vascular endothelial cells and in stromal cells surrounding blood vessels. Two discrete immunostaining patterns were observed in high‐grade PIN. VEGF expression of low‐to‐moderate intensity was defined as pattern A. The other, characterized by a strong cytoplasmic immunoreaction similar to that of poorly differentiated tumors, was defined as pattern B. The capillary architecture in high‐grade PIN with pattern A was similar to the orderly vascular network seen in normal prostates, whereas in the pattern B it had the characteristics of microvessels usually seen in PCa. The degree of vascularization in the stroma adjacent to intensely VEGF‐stained cells (neuroendocrine phenotype) was higher than that noted in association with secretory cells. CAB before surgery downregulated the expression of VEGF and decreased the degree of vascularization, except in the cell areas with neuroendocrine (NE) features. CONCLUSIONS Our immunohistochemical results indicate that significant levels of VEGF are present in prostate cancer and in a population of PIN lesions, expression being highest in association with NE cells. VEGF expression is downregulated by hormonal manipulation, except in the population of NE cells. Prostate 45:72–79, 2000. © 2000 Wiley‐Liss, Inc.

Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target.

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