Increased soluble CD44 concentrations are associated with larger tumor size and lymph node metastasis in breast cancer patients |
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Authors: | Sebastian Mayer Axel zur Hausen Dirk Otto Watermann Stefan Stamm Markus Jäger Gerald Gitsch Elmar Stickeler |
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Institution: | (1) Department of Obstetrics and Gynaecology, University Hospital Freiburg, Freiburg, Germany;(2) Institute of Pathology, University Hospital Freiburg, Freiburg, Germany;(3) Institute of Biochemistry FAU, Erlangen, Germany |
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Abstract: | Purpose CD44 is a cell surface glycoprotein involved in cell–cell and cell–substrate interactions, which may be shed or released into
circulation by proteolytic enzymatic mechanisms. Alternative splicing of CD44 and aberrant levels of soluble CD44 variants
in the serum of cancer patients have been correlated to tumor progression and metastasis in different tumors including breast
cancer. In this study we evaluated the clinical value of CD44 serum levels (sCD44) in patients with primary breast cancer.
Methods Concentrations of soluble isoforms sCD44std, sCD44v5 and sCD44v6 were determined with a sensitive ELISA and normalized against
the total protein concentration (TP). Pre-operative serum samples from 82 patients and 67 age-matched healthy blood donors
were analyzed. The results were correlated to clinico-pathological parameters (tumor size, grading, lymph node metastasis,
etc.).
Results In sera of breast cancer patients, we detected elevated concentrations of sCD44v6 (P = 0.0001) and total protein TP (P = 0.0001) in comparison to healthy controls, whereas overall sCD44 (sCD44std) and sCD44v5 did not differ. Patients with sCD44v6-concentrations
above the 75%-percentile showed an increased T stage (2.9 cm vs. 1.8 cm) as well as a higher risk for lymph node metastasis
(55% vs. 35%). In breast cancer patients with lymph node metastasis the median value of sCD44v6 was significantly higher (P = 0.025) in comparison to patients without lymph node metastasis and healthy controls.
Conclusions Our data suggest an upregulated expression of alternatively spliced soluble CD44 isoforms in breast cancer patients. The specific
alterations of certain CD44 isoform concentrations (especially sCD44v6) may reflect disturbances of the nuclear splicing machinery
in tumor cells. The clinical significance of our findings are underlined by the positive correlation of elevated sCD44v6 concentrations
and lymph node metastases (r
s = 0.25). |
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Keywords: | Soluble CD44 Primary breast cancer Tumor size Lymph node metastasis |
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