Alternative splicing of CD44 and aberrant levels of soluble CD44 protein in
the serum of cancer patients has been correlated to tumor progression and
metastasis. To examine the clinical value of CD44 serum levels (sCD44) in o
varian cancer we determined concentrations of the soluble, variable isoform
s sCD44std, sCD44v5 and sCD44v6 with a sensitive ELISA. Pre-operative serum
samples from 66 patients with histologically diagnosed invasive disease as
well as sera taken from 40 healthy blood donors were analyzed. In sera of
ovarian cancer patients we detected elevated concentrations of overall CD44
serum levels represented by sCD44std (p=0.001), but decreased levels of th
e specific isoforms CD44v5 (p=0.0002) and v6 (p=0.0001). This is the first
report demonstrating that ovarian cancer patients with pelvic lymph node me
tastasis at the time of diagnosis showed specifically elevated sCD44v6 (p=0
.073) serum concentrations in comparison to patients without lymph node inv
olvement, whereas overall sCD44 serum levels did not differ. Decreased seru
m levels of sCD44v5 were found in progesterone receptor-positive tumors (p=
0.059) and postmenopausal patients (p=0.032). Increased concentrations of s
CD44v6 were detectable in estrogen receptor-positive tumors but not signifi
cantly (p=0.138). Serum CD44v5 levels were associated with shortened relaps
e-free survival time. No association was found between serum CD44 isoforms
and the classical clinicopathological parameters stage and grading or overa
ll survival. CD44 splice variants are possibly involved in a complex intera
ction with the hormonal environment during tumorigenesis and metastasis of
ovarian cancer.