Affiliations: Department of General and Transplant Surgery,
Innsbruck Medical University, Austria | Laboratory of Tumor Biology & Angiogenesis,
Department of Hematology and Oncology, Innsbruck Medical University,
Austria | Tyrolean Cancer Research Institute, Innsbruck,
Austria | Department of Pathology, Innsbruck Medical University,
Austria | Department of Pathology, Basel University Hospital,
Switzerland
Note: [] Corresponding author: Matthias Zitt, MD, Department of General
and Transplant Surgery, Innsbruck Medical University, Anichstrasse 35, A-6020
Innsbruck, Austria. Tel.: +43 512 504 0; Fax: +43 512 504 28519; E-mail:
matthias.zitt@i-med.ac.at
Abstract: Gene expression of Dickkopf-3 (Dkk-3) has been shown to be
upregulated in tumor endothelium of colorectal cancer (CRC). For the first
time, we analyzed Dkk-3 protein expression in CRC and its potential as a marker
for neoangiogenesis. We used tissue microarrays (TMAs) to investigate Dkk-3 in
microvessels of 403 CRC samples, 318 appropriate adjacent non-cancerous samples
and 127 normal colorectal samples. Of cancer samples with CD31-positive
microvessels, 67.7% were positive for Dkk-3. Dkk-3 staining was demonstrated
in endothelial cells of all microvessels in nearly all cases.
Dkk-3-positive samples showed a higher mean microvessel count than did
Dkk-3-negative samples (P=0.001). Dkk-3 expression increased with rising
numbers of microvessels per sample (P<0.0001). In adjacent samples with
CD31-positive microvessels, 56% were Dkk-3-positive in all
microvessels. Similar to cancer samples, Dkk-3-positive adjacent samples had a
higher mean microvessel count than did Dkk-3-negative samples (P<0.0001),
and Dkk-3 expression also increased with rising numbers of
microvessels (P<0.0001). All microvessels in normal mucosa samples were
negative for Dkk-3. Dkk-3 can be considered a putative pro-angiogenic protein
in neovascularization and may possibly be a marker for neoangiogenesis in CRC.
Further investigations will elucidate whether Dkk-3 is a target structure for
novel therapies.
