title: Clinical significance of vascular endothelial growth factors (VEGF)-C and -D in resected non-small cell lung cancer.
abstract: OBJECTIVE
  Lymphatic spread of tumor is an important prognostic factor for patients with non-small cell lung carcinoma (NSCLC). Vascular endothelial growth factor-C (VEGF-C) and VEGF-D play important roles in lymphangiogenesis via the VEGF receptor 3 (VEGFR-3). We sought to determine whether VEGF-C, VEGF-D and VEGFR-3 are involved in the clinical outcomes of patients with resected NSCLC.
  
  
  METHODS
  Using immunohistochemical staining, we investigated the protein expressions of VEGF-C, VEGF-D and VEGFR-3 in the tissue array specimens from patients who underwent resection for NSCLC. The immunoreactivity for p53 was also examined. The clinicopathological implications of these molecules were statistically analyzed.
  
  
  RESULTS
  Analysis of a total of 118 specimens showed that VEGF-C, VEGF-D and their co-expression were significantly associated with more advanced regional lymph node metastasis (p=0.019, p=0.044 and p=0.026, respectively, N2 versus N0 and N1). A VEGFR-3 expression had a strong correlation with peritumoral lymphatic invasion (p=0.047). On the multivariate analysis for survival and recurrence, pathologic N2 lymph node metastasis was the only independent prognostic factor, but none of the investigated molecules showed any statistical correlation with recurrence and survival.
  
  
  CONCLUSIONS
  The present study revealed that high expressions of VEGF-C and VEGF-D were strongly associated with more advanced regional lymph node metastasis in patients with resected NSCLC.
authors.affiliation: Division of Oncology, Department of Internal Medicine, Kangnam St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Yoon Ho
authors.initials: YH
authors.lastname: Ko
authors.forename: Chan-Kwon
authors.initials: CK
authors.lastname: Jung
authors.forename: Myung-Ah
authors.initials: MA
authors.lastname: Lee
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Byun
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kang
authors.forename: Kyo Young
authors.initials: KY
authors.lastname: Lee
authors.forename: Keon Hyun
authors.initials: KH
authors.lastname: Jo
authors.forename: Young Pil
authors.initials: YP
authors.lastname: Wang
authors.forename: Young Seon
authors.initials: YS
authors.lastname: Hong
references.citation: Cancer. 2003 Jan 15;97(2):457-64
references.pmid: 12518370
references.citation: Respirology. 2005 Jan;10(1):31-5
references.pmid: 15691235
references.citation: Cancer Res. 2002 Mar 15;62(6):1669-75
references.pmid: 11912138
references.citation: Onkologie. 2005 May;28(5):281-8
references.pmid: 15867486
references.citation: Anticancer Res. 2005 Jul-Aug;25(4):3003-9
references.pmid: 16080559
references.citation: Br J Cancer. 2003 Jan 27;88(2):237-44
references.pmid: 12610509
references.citation: Lung Cancer. 2001 Aug-Sep;33(2-3):125-32
references.pmid: 11551407
references.citation: Eur J Surg Oncol. 2007 Apr;33(3):294-300
references.pmid: 17129704
references.citation: Am J Pathol. 2007 Apr;170(4):1348-61
references.pmid: 17392173
references.citation: Prostate. 2005 Oct 1;65(2):110-6
references.pmid: 15880525
references.citation: Cancer Res Treat. 2003 Aug;35(4):279-80
references.pmid: 26680947
references.citation: Exp Mol Pathol. 2005 Apr;78(2):123-30
references.pmid: 15713437
references.citation: Cancer. 1999 Nov 15;86(10):1976-84
references.pmid: 10570421
references.citation: Pathol Res Pract. 2005;201(2):93-9
references.pmid: 15901129
references.citation: Pathol Int. 2007 Apr;57(4):171-7
references.pmid: 17316411
references.citation: Ann Thorac Surg. 2006 Oct;82(4):1198-204
references.pmid: 16996907
references.citation: Chest. 1997 Jun;111(6):1710-7
references.pmid: 9187198
references.citation: Cancer Res. 1991 Oct 1;51(19):5232-7
references.pmid: 1717142
references.citation: J Clin Oncol. 2006 Jan 10;24(2):228-40
references.pmid: 16344322
references.citation: Int J Clin Oncol. 2005 Oct;10(5):318-27
references.pmid: 16247658
references.citation: Lung Cancer. 2004 Sep;45(3):325-37
references.pmid: 15301873
references.citation: Am J Pathol. 1999 May;154(5):1381-90
references.pmid: 10329591
references.citation: Cancer Res. 2000 Jan 15;60(2):203-12
references.pmid: 10667560
references.citation: Nat Rev Cancer. 2002 Aug;2(8):573-83
references.pmid: 12154350
references.citation: Cancer Res. 2004 Dec 15;64(24):9027-34
references.pmid: 15604268