title: Immunohistochemically detectable dickkopf-3 expression in tumor vessels predicts survival in gastric cancer.
abstract: Dickkopf-3 (Dkk-3) may act as a tumor suppressor as it is downregulated in various types of cancer. Moreover, a putative role in tumor neovascularization is discussed. Here, we investigated the expression of Dkk-3 protein in gastric cancer and its potential value as a prognostic marker. Dkk-3 expression was analyzed by immunohistochemistry in 136 tumor samples and was correlated with microvessel density (MVD), tumor stage, and grading as well as the clinical outcome of the patients. Dkk-3 expression was detected in endothelial cells of the tumor vessels in 129/136 (94.9%) and in tumor cells in 85/136 (62.5%) samples. MVD was high and low in 57 (42.9%) and 76 (57.1%) specimens respectively. In tumor cells, overexpression of Dkk-3 was found in 41 (30.1%) of all cases and was correlated significantly to pT-stage (p < 0.05) and UICC stage (p < 0.05). Survival analysis regarding Dkk-3 expression in tumor endothelial cells showed that Dkk-3 is an independent predictor of disease-free survival (p < 0.05). Dkk-3 expression in tumor vessels of patients with gastric cancer identifies a population of patients with relatively favorable prognosis.
authors.affiliation: Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Mühlmann
authors.forename: Gerold
authors.initials: G
authors.lastname: Untergasser
authors.forename: Matthias
authors.initials: M
authors.lastname: Zitt
authors.forename: Marion
authors.initials: M
authors.lastname: Zitt
authors.forename: Hans
authors.initials: H
authors.lastname: Maier
authors.forename: Gregor
authors.initials: G
authors.lastname: Mikuz
authors.forename: Irmgard E
authors.initials: IE
authors.lastname: Kronberger
authors.forename: Michael C
authors.initials: MC
authors.lastname: Haffner
authors.forename: Eberhard
authors.initials: E
authors.lastname: Gunsilius
authors.forename: Dietmar
authors.initials: D
authors.lastname: Ofner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000098:blood supply / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018925:Chemokines; D042783:Endothelial Cells / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D013274:Stomach Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000401:mortality / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins
references.citation: Science. 2000 Aug 18;289(5482):1197-202
references.pmid: 10947988
references.citation: Nat Rev Cancer. 2008 Aug;8(8):579-91
references.pmid: 18596824
references.citation: Cell. 1996 Aug 9;86(3):353-64
references.pmid: 8756718
references.citation: J Clin Oncol. 2003 Jun 15;21(12):2234-6
references.pmid: 12805321
references.citation: Int J Cancer. 2008 Apr 1;122(7):1539-47
references.pmid: 18033687
references.citation: Gene. 2003 Jan 2;302(1-2):179-83
references.pmid: 12527209
references.citation: J Surg Oncol. 1997 Aug;65(4):232-6
references.pmid: 9274786
references.citation: Nature. 2002 Jun 6;417(6889):664-7
references.pmid: 12050670
references.citation: Dis Markers. 2008;24(2):101-9
references.pmid: 18219095
references.citation: J Urol. 2004 Mar;171(3):1314-8
references.pmid: 14767340
references.citation: Lancet. 2003 Jul 26;362(9380):305-15
references.pmid: 12892963
references.citation: Oncogene. 2006 Oct 19;25(49):6528-37
references.pmid: 16751809
references.citation: N Engl J Med. 1991 Jan 3;324(1):1-8
references.pmid: 1701519
references.citation: Biochem Biophys Res Commun. 2000 Feb 5;268(1):20-4
references.pmid: 10652205
references.citation: Br J Cancer. 2004 Aug 16;91(4):707-13
references.pmid: 15226763
references.citation: Cancer Sci. 2009 Aug;100(8):1414-20
references.pmid: 19493271
references.citation: Oncogene. 2009 Oct 1;28(39):3442-55
references.pmid: 19633687
references.citation: Eur J Cancer. 1999 Jul;35(7):1059-64
references.pmid: 10533448
references.citation: Cancer Res. 2005 May 15;65(10):4218-27
references.pmid: 15899813
references.citation: Gene. 2002 Jan 9;282(1-2):151-8
references.pmid: 11814687
references.citation: Oncogene. 2006 Aug 17;25(36):5027-36
references.pmid: 16568085
references.citation: Lancet. 2000 Dec 9;356(9246):1981-2
references.pmid: 11130529
references.citation: N Engl J Med. 1971 Nov 18;285(21):1182-6
references.pmid: 4938153
references.citation: N Engl J Med. 2001 Sep 6;345(10):725-30
references.pmid: 11547741
references.citation: N Engl J Med. 2006 Jul 6;355(1):11-20
references.pmid: 16822992
references.citation: Oncogene. 2006 Dec 4;25(57):7469-81
references.pmid: 17143291
references.citation: Ann Surg. 2003 Jul;238(1):9-28
references.pmid: 12832961
references.citation: Cancer. 2009 Jan 1;115(1):49-60
references.pmid: 19051296
references.citation: Int J Oncol. 2001 Jul;19(1):117-21
references.pmid: 11408931
references.citation: Gene. 1999 Oct 1;238(2):301-13
references.pmid: 10570958