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. 2021 Dec 11;10(24):5795.
doi: 10.3390/jcm10245795.

Immunohistochemical Expression of Wnt-4 Protein in Clear Cell Renal Carcinoma

Oliver Pavlovic  1   2 , Tvrtko Hudolin  3   4 , Ivan Miskulin  5 , Stela Bulimbasic  4   6 , Marijana Coric  4   6 , Josip Perkovic  1   2 , Toni Zekulic  3
Affiliations

Immunohistochemical Expression of Wnt-4 Protein in Clear Cell Renal Carcinoma

Oliver Pavlovic et al. J Clin Med. .

Abstract

Wingless binding integration site proteins (Wnt) have an important role in normal kidney development and in various kidney diseases. They are required for complete epithelial differentiation and normal nephron formation. Changes in these proteins could also have important role in carcinogenesis. This study included 185 patients with clear cell renal carcinoma (ccRCC) in whom immunohistochemical expression of Wnt-4 protein in healthy and tumorous tissue after surgery was investigated. There was higher expression of Wnt-4 in healthy than in tumor tissue. No difference between Fuhrman's grade and Wnt-4 expression was found. A poor negative correlation between tumor size and Wnt-4 expression was found. Patients with suspected metastatic diseases had higher Wnt-4 expression. There was no difference in survival rates between Wnt-4 negative and positive groups. In our study we have shown that high Wnt-4 expression in healthy tissue decreases in low-grade tumors but then increases in high-grade tumors, suggesting that tumor progression requires Wnt-4 activation or reactivation.

Keywords: Wnt signaling pathway; Wnt-4 protein; clear cell renal carcinoma; immunohistochemistry.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Immunohistochemical stain for Wnt-4: (a) strong and uniform cytoplasmic Wnt-4 positivity in tubular epithelial cells. Podocytes along the glomerular tuft and Bowman’s parietal epithelial cells are also positive for Wnt-4 (magnification 200×); (b) a weak cytoplasmic positivity in tumor cells for Wnt-4 (magnification 400×); (c) a moderate cytoplasmic staining of the tumor cells for Wnt-4 (magnification 400×); (d) diffuse, strong cytoplasmic staining for Wnt-4 of the tumor cells (magnification 200×).
Figure 1
Figure 1
Immunohistochemical stain for Wnt-4: (a) strong and uniform cytoplasmic Wnt-4 positivity in tubular epithelial cells. Podocytes along the glomerular tuft and Bowman’s parietal epithelial cells are also positive for Wnt-4 (magnification 200×); (b) a weak cytoplasmic positivity in tumor cells for Wnt-4 (magnification 400×); (c) a moderate cytoplasmic staining of the tumor cells for Wnt-4 (magnification 400×); (d) diffuse, strong cytoplasmic staining for Wnt-4 of the tumor cells (magnification 200×).
Figure 2
Figure 2
Correlation of Wnt-4 expression and tumor grade. Due to the small number of patients, grades 1 and 4 are excluded (neg; no immunohistochemical staining, (+) weak; (++) moderate; (+++) strong immunohistochemical staining).
Figure 3
Figure 3
Wnt-4 expression in patients with and without metastases. There is a difference between the groups, but due to the large difference in the number of patients with and without metastases it is not significant (SE; standard error).
Figure 4
Figure 4
Cumulative proportion surviving of Wnt-4 negative and Wnt-4 positive groups.
See this image and copyright information in PMC

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