YKL-40 expression in naevocellular naevi, carcinomas and melanomas of the skin

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18019-18019 ◽  
Author(s):  
H. Schmidt ◽  
A. Roslind ◽  
J. S. Johansen ◽  
D. L. Nielsen ◽  
P. A. Price ◽  
...  

18019 Background: Elevated serum levels of the protein YKL-40 are associated with a poor prognosis in several solid tumors including melanoma (H. Schmidt, JCO 2006, Cancer 2006 in press). YKL-40 is secreted by cancer cells, macrophages and neutrophils. The function of YKL-40 is only poorly understood. It may be a growth or differentiation factor, play a role in angiogenesis or protect against apoptosis. The aim was to describe the tissue expression of YKL-40 in naevocellular naevi, carcinomas and melanomas of the skin by immunohistochemistry. Methods: Paraffin-embedded tissue sections from 40 patients with different naevocellular naevi, carcinomas and melanomas of the skin were developed with EnVision+ System-HRP K4007 (DakoCytomation) using a monoclonal antibody against YKL-40. The intensity of YKL-40 staining was scored using a semi-quantitative method. Results: YKL-40 protein expression appeared as a cytoplasmic, granular staining with no staining of membranes, nuclei or extracellular matrix. In normal skin the basal epithelial layer stained weakly positive. Melanocytes and melanophages stained negative. Macrophages and leucocytes stained positive. Hair follicles, sebaceous glands and sweat glands stained positive. Three basal cell carcinomas all stained positive. In 10 squamous cell carcinomas, the epidermal components stained positive and the invasive tumor islands were negative. In 3 keratoacanthomas, the epithelial components as well as the infiltrative tumor islands stained positive. In naevi (2 junctional, 5 compound and 1 intradermal) the epithelial components stained positive, the intradermal components stained negative. In melanomas the tumor cells stained positive in 9 of 10 specimens. Both the epidermal and the invasive components of melanomas stained positive. Three melanoma metastases all stained positive. Conclusions: YKL-40 is expressed in normal skin and in benign and malignant lesions of the skin. Generally, YKL-40 expression is increased in cells of high activity, although the invasive tumor islands of squamous cell carcinomas stain negative. In melanomas, the tumor cells may be a source of the elevated YKL-40 serum levels observed in these patients. No significant financial relationships to disclose.

Head & Neck ◽  
2014 ◽  
Vol 37 (10) ◽  
pp. 1477-1482 ◽  
Author(s):  
Seraina Denoth ◽  
Martina A. Broglie ◽  
Stephan K. Haerle ◽  
Gerhard F. Huber ◽  
Sarah R. Haile ◽  
...  

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2908-2908
Author(s):  
Murat O. Arcasoy ◽  
Khalid Amin ◽  
Shu-Chuan Chou ◽  
Zishan A. Haroon ◽  
Mahesh Varia ◽  
...  

Abstract Erythropoietin (EPO), an oxygen-regulated glycoprotein hormone, is a hematopoietic cytokine that stimulates erythropoiesis by binding to its cellular receptor EPOR. The recombinant form of human EPO is widely used in clinical practice for the prevention or treatment of anemia associated with cancer and chemo-radiation therapy. However, in a recent randomized, placebo-controlled trial involving patients receiving curative radiotherapy for squamous cell carcinoma of the head and neck, EPO treatment was associated with poorer loco-regional progression-free survival. The purpose of this study was to determine whether EPOR and its ligand EPO are expressed in primary squamous cell carcinomas of the head and neck. We also investigated the hypothesis that EPO expression in malignant cells may be associated with the presence of tumor hypoxia, an important factor involved in resistance to radiation treatment, tumor aggressiveness and poor prognosis. Twenty-one patients with squamous cell carcinoma of the head and neck were enrolled in a tumor hypoxia study under a research protocol approved by the Institutional Review Board at the University of North Carolina Hospitals. All patients provided signed informed consent. The patients received an intravenous infusion of the hypoxia marker pimonidazole hydrochloride (Hypoxyprobe-1™) prior to multiple tumor biopsies. Two or more biopsies were available from all except one primary tumor. The tissue specimen from one patient with laryngeal carcinoma was excluded because of availability of only a single, small and fragmented biopsy. Contiguous sections from 74 biopsies were analyzed by immunohistochemistry for expression of EPOR and EPO as well as pimonidazole binding. We found EPOR expression in tumor cells in 97% of the biopsies. The pattern of EPOR immunoreactivity was predominantly cytoplasmic but was found to be localized to the membrane in some sections. Co-expression of EPO was observed in 90% of biopsies. Qualitative and semi-quantitative analyes for EPO staining and tumor hypoxia on a section-by-section basis revealed that EPO and pimonidazole adduct staining did not always co-localize within tumors but there was a significant positive correlation between levels of micro-regional EPO expression and pimonidazole binding (r = 0.736, P < 0.001, n=20 by two-tailed Spearman’s rank correlation analysis). These data demonstrate the co-expression of EPOR and its ligand EPO in squamous carcinoma cells suggesting that EPO may play a novel role as a potential autocrine or paracrine growth factor in head and neck cancer. Furthermore, EPO expression in tumor cells may be modulated, at least in part, by tumor hypoxia. The expression of EPOR needs to be taken into consideration in the design of future clinical trials investigating the role of recombinant human EPO in head and neck cancer.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10599-10599 ◽  
Author(s):  
Volkmar Mueller ◽  
Sabine Riethdorf ◽  
Brigitte Kathrin Rack ◽  
Wolfgang Janni ◽  
Peter A. Fasching ◽  
...  

10599 Background: Circulating tumor cells (CTC) reflect an aggressive tumor behavior by hematogenous tumor cell dissemination. Overexpression of HER2 in breast cancer (BC) is associated with increased angiogenesis and therefore potentially linked to increased hematogenous tumor cell spread. The aim of the analysis was to investigate whether concentrations of serum HER2 (sHER2) deliver prognostic information in the context of CTC detection in metastatic BC patients. Methods: Blood was obtained in a prospective multicenter setting from 254 patients with metastatic BC at the time of disease progression. sHER2 was determined using a commercial ELISA-kit (Wilex). CTC were detected with the CellSearch system (Veridex). Patients received systemic treatment according to national and international guidelines including HER2-targeted treatment. Results: Five or more CTC were detected in 122 of 245 evaluable patients (49.8%).119 of 251 (47%) metastatic patients had serum sHER2 levels above 15ng/mL. Median PFS was 9.2 months (95%-CI: 9.9 – 13.0 mths) with elevated sHER2 versus 11.4 mths (9.9 – 13.0 mths) with non-elevated levels (p=0.07). OS was 17.4 mths (14.6 – 20.3 mths) vs. 26.5 mths (23.1-29.8 mths; p<0.01). In patients with 5 or more CTC, serum levels were above the cut-off for sHER2 in 61% vs. 33% in those with less than 5 CTC (p< 0.01). Patients with elevated sHER and 5 or more CTC hat a PFS of 9.1 mths (7.2 – 11.1 mths) and a OS of 14.5 mths (11.8 – 17.2 mths), those with non-elevated sHER2 and less than 5 CTC a PFS of 12.1 (10.1 – 14.1 mths) and a OS of 29.5 month (25.4 – 33.6 mths) (p=0.15 for PFS and p< 0.01 for OS). Including sHER2, CTC and established prognostic factors in the multivariate analysis, the presence of CTC, line of therapy, ER and HER2 status of the primary tumor remained independent predictors of OS. Conclusions: Elevated serum levels of sHER2 are associated with the presence of CTC and indicate poor clinical outcome. However, sHER2 has no independent prognostic value when presence of CTC were taken into account.


2004 ◽  
Vol 64 (21) ◽  
pp. 8057-8061 ◽  
Author(s):  
Jochen Karcher ◽  
Gerhard Dyckhoff ◽  
Philipp Beckhove ◽  
Christoph Reisser ◽  
Michael Brysch ◽  
...  

2019 ◽  
Vol 39 (9) ◽  
pp. 5171-5177
Author(s):  
DAVID KALFERT ◽  
JAROSLAV LUDVIK ◽  
RADEK KUCERA ◽  
ONDREJ TOPOLCAN ◽  
PETR CELAKOVSKY ◽  
...  

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