title: Angiogenesis in cancer of unknown primary: clinicopathological study of CD34, VEGF and TSP-1.
abstract: BACKGROUND
  Cancer of unknown primary remains a mallignancy of elusive biology and grim prognosis that lacks effective therapeutic options. We investigated angiogenesis in cancer of unknown primary to expand our knowledge on the biology of these tumors and identify potential therapeutic targets.
  
  
  METHODS
  Paraffin embedded archival material from 81 patients diagnosed with CUP was used. Tumor histology was adenocarcinoma (77%), undifferentiated carcinoma (18%) and squamous cell carcinoma (5%). The tissue expression of CD34, VEGF and TSP-1 was assessed immunohistochemically by use of specific monoclonal antibodies and was analyzed against clinicopathological data.
  
  
  RESULTS
  VEGF expression was detected in all cases and was strong in 83%. Stromal expression of TSP-1 was seen in 80% of cases and was strong in 20%. The expression of both proteins was not associated with any clinical or pathological parameters. Tumor MVD was higher in tumors classified as unfavorable compared to more favorable and was positively associated with VEGF and negatively with TSP-1.
  
  
  CONCLUSIONS
  Angiogenesis is very active and expression of VEGF is almost universal in cancers of unknown primary. These findings support the clinical investigation of VEGF targeted therapy in this clinical setting.
authors.affiliation: Medical Oncology Department, Ioannina University Hospital, Ioannina, Greece. vasilios.karavasilis@rmh.nhs.uk <vasilios.karavasilis@rmh.nhs.uk>
authors.forename: Vasilis
authors.initials: V
authors.lastname: Karavasilis
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Malamou-Mitsi
authors.forename: Evangelos
authors.initials: E
authors.lastname: Briasoulis
authors.forename: Elena
authors.initials: E
authors.lastname: Tsanou
authors.forename: Evangelia
authors.initials: E
authors.lastname: Kitsou
authors.forename: Haralambos
authors.initials: H
authors.lastname: Kalofonos
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
authors.forename: Theodore
authors.initials: T
authors.lastname: Fotsis
authors.forename: Nicholas
authors.initials: N
authors.lastname: Pavlidis
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000737:chemistry / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology / Q000556:secondary / Q000628:therapy; D002277:Carcinoma / Q000098:blood supply / Q000737:chemistry / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology / Q000628:therapy; D009389:Neovascularization, Pathologic; D019700:Thrombospondin 1 / Q000032:analysis*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D019700:Thrombospondin 1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
references.citation: Eur J Cancer. 2003 Sep;39(14):1990-2005
references.pmid: 12957453
references.citation: Eur J Cancer. 2002 Feb;38(3):409-13
references.pmid: 11818207
references.citation: Ann Intern Med. 1986 Apr;104(4):547-53
references.pmid: 3006571
references.citation: World J Surg. 2004 Jun;28(6):535-9
references.pmid: 15366740
references.citation: Br J Cancer. 2000 Aug;83(3):298-306
references.pmid: 10917542
references.citation: Clin Cancer Res. 2001 Sep;7(9):2826-31
references.pmid: 11555600
references.citation: Ann Oncol. 2003 Feb;14(2):191-6
references.pmid: 12562643
references.citation: Br J Cancer. 1996 Apr;73(7):931-4
references.pmid: 8611409
references.citation: Anticancer Res. 2004 Jan-Feb;24(1):297-301
references.pmid: 15015611
references.citation: Cancer Res. 2000 Jun 1;60(11):2898-905
references.pmid: 10850435
references.citation: Ann Oncol. 1992 Sep;3(8):631-4
references.pmid: 1450045
references.citation: Oncologist. 1997;2(3):142-152
references.pmid: 10388044
references.citation: Int J Cancer. 1997 Feb 20;74(1):81-5
references.pmid: 9036874
references.citation: J Clin Oncol. 2002 Dec 15;20(24):4679-83
references.pmid: 12488413
references.citation: Nat Rev Drug Discov. 2004 May;3(5):391-400
references.pmid: 15136787
references.citation: Science. 1989 Dec 8;246(4935):1306-9
references.pmid: 2479986
references.citation: Eur J Cancer. 2002 Sep;38(13):1810-2
references.pmid: 12175699
references.citation: J Clin Oncol. 1994 Jun;12(6):1272-80
references.pmid: 8201389
references.citation: Anticancer Res. 1998 May-Jun;18(3B):1907-14
references.pmid: 9677443
references.citation: Clin Cancer Res. 1999 Nov;5(11):3403-10
references.pmid: 10589751
references.citation: Int J Biochem Cell Biol. 2004 Jun;36(6):1070-8
references.pmid: 15094121
references.citation: Anticancer Res. 1995 Nov-Dec;15(6B):2563-7
references.pmid: 8669824
references.citation: J Natl Cancer Inst. 1997 Feb 5;89(3):219-27
references.pmid: 9017002
references.citation: Ann Intern Med. 1989 Aug 1;111(3):213-7
references.pmid: 2502058
references.citation: Nat Rev Cancer. 2002 Oct;2(10):795-803
references.pmid: 12360282