Secreted
frizzled-related protein 3 (SFRP3) is a member of the family of soluble
proteins, which modulate the Wnt signaling cascade. Novel research has identified aberrant expression of
SFRPs in different types of
cancer. In the present study the expression intensities and localizations of the SFRP3
protein across different histopathological grades of astrocytic
brain tumors were investigated by immunohistochemistry, digital scanning and image analysis. The results demonstrated that the differences between expression levels and
malignancy grades were statistically significant.
Tumors were classified into four
malignancy grades according to the World Health Organization guidelines. Moderate (P=0.014) and strong (P=0.028) nuclear expression levels were significantly different in pilocytic (grade I) and diffuse (grade II)
astrocytomas demonstrating higher expression values, as compared with
anaplastic astrocytoma (grade III) and
glioblastoma (grade IV). When the sample was divided into two groups, the moderate and high cytoplasmic expression levels were observed to be significantly higher in
glioblastomas than in the group comprising astrocytoma II and III. Furthermore, the results indicated that high grade
tumors were associated with lower values of moderate (P=0.002) and strong (P=0.018) nuclear expression in comparison to low grade
tumors. Analysis of cytoplasmic staining demonstrated that strong cytoplasmic expression was significantly higher in the astrocytoma III and IV group than in the astrocytoma I and II group (P=0.048). Furthermore, lower grade
astrocytomas exhibited reduced membranous SFRP3 staining when compared with higher grade
astrocytomas and this difference was statistically significant (P=0.036). The present results demonstrated that SFRP3
protein expression levels were decreased in the nucleus in higher grade
astrocytoma (indicating the expected behavior of an antagonist of Wnt signaling), whereas when the SFRP3 was located in the cytoplasm an increased expression level of SFRP3 was identified in the high grade
astrocytomas when compared with those of a low grade. This may suggest that SFRP3 acts as an agonist of Wnt signaling and promotes invasive behavior.