title: Human epidermal growth factor receptor-2 expression in primary and metastatic gastric cancer.
abstract: BACKGROUND
  Amplification and overexpression of human epidermal growth factor receptor-2 (HER-2) has been shown in subgroups of gastric cancer, correlated to more aggressive disease and predictive for the treatment with HER-2 antibodies. In this study, we examined the prognostic value of HER-2 expression in primary gastric cancer and in associated lymph node metastases and confirmed the role of HER-2 in tumor angiogenesis by examining vascular endothelial growth factor (VEGF) expression.
  
  
  METHODS
  Immunohistochemistry was used to detect HER-2 and VEGF expression in 110 gastric cancer specimens and associated lymph node metastases and in 96 specimens of normal gastric mucosa.
  
  
  RESULTS
  The expression level of HER-2 in gastric tissues was significantly higher than in normal tissues (19.1 % vs. 8.3 %; P < 0.05). HER-2 overexpression was homogeneous in primary gastric cancer and metastatic lymph nodes (P = 0.607). There was a significant positive correlation of HER-2 expression and VEGF expression (P = 0.007). HER-2 overexpression in primary tumor correlated with lymph node metastasis, distant metastasis, and American Joint Committee on Cancer (AJCC) stage. Cox regression multivariate analyses confirmed that tumor size, histological grade, lymph node ratio, AJCC stage, chemotherapy, and HER-2 expression were all prognostic factors. Patients with HER-2 positivity in both primary and metastatic tissues (+/+) had the poorest survival (OS, 12.5 months; DFS, 11.0 months) (P < 0.01).
  
  
  CONCLUSIONS
  HER-2 was significantly overexpressed in gastric cancer versus normal tissue and correlated with VEGF expression. HER-2 in tumor or lymph nodes was an independent negative prognostic factor.
authors: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road #300, 210029, Nanjing, Jiangsu, China.
authors: Yiting
authors: Y
authors: Geng
authors: Xiaofeng
authors: X
authors: Chen
authors: Jinrong
authors: J
authors: Qiu
authors: Yue
authors: Y
authors: Zhou
authors: Jian
authors: J
authors: Wang
authors: Lingxiang
authors: L
authors: Liu
authors: Yongfeng
authors: Y
authors: Shao
authors: Yongmei
authors: Y
authors: Yin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D042461:Vascular Endothelial Growth Factor A; C508053:ERBB2 protein, human
references: Ann Oncol. 2007 Jun;18 Suppl 6:vi11-5
references: 17591801
references: Cancer Res. 2001 Jul 15;61(14):5345-8
references: 11454672
references: J Gastroenterol Hepatol. 2007 Aug;22(8):1317-21
references: 17559372
references: Br J Cancer. 2011 Apr 26;104(9):1372-6
references: 21487407
references: Ann Oncol. 2010 May;21(5):955-60
references: 19940005
references: Eur J Surg Oncol. 2008 May;34(5):519-24
references: 17624713
references: Curr Drug Targets. 2005 May;6(3):243-57
references: 15857286
references: Cancer Lett. 2005 Sep 8;227(1):9-23
references: 16051028
references: Cancer. 2007 Sep 15;110(6):1195-200
references: 17647266
references: J Clin Oncol. 2000 Jun;18(11):2201-9
references: 10829039
references: Clin Cancer Res. 2004 Mar 1;10(5):1706-16
references: 15014023
references: Gastric Cancer. 1998 Dec;1(1):10-24
references: 11957040
references: Lancet. 2010 Aug 28;376(9742):687-97
references: 20728210
references: Histopathology. 2008 Jun;52(7):797-805
references: 18422971
references: Cancer. 2005 May 1;103(9):1763-9
references: 15786420
references: Dis Esophagus. 2013 Apr;26(3):299-304
references: 22676551
references: Oncol Rep. 2006 Jan;15(1):65-71
references: 16328035
references: Int J Cancer. 2008 Mar 1;122(5):999-1004
references: 17973263
references: Ann Oncol. 2012 Oct;23(10):2656-2662
references: 22689179
references: Nat Rev Cancer. 2005 May;5(5):341-54
references: 15864276
references: Pathol Oncol Res. 2013 Jan;19(1):103-9
references: 22907801
references: Ann Oncol. 2005 Feb;16(2):273-8
references: 15668283
references: Clin Cancer Res. 2004 Jun 15;10(12 Pt 1):4083-8
references: 15217943
references: World J Surg. 2009 Oct;33(10):2112-8
references: 19636613
references: Ann Clin Lab Sci. 2000 Jul;30(3):259-65
references: 10945565
references: Breast Cancer Res Treat. 2009 Jan;113(2):301-6
references: 18273700
references: Ann Oncol. 2002 Jul;13(7):1036-43
references: 12176781
references: Oncologist. 2012;17(4):469-75
references: 22467666
references: Eur J Surg Oncol. 2008 Feb;34(2):159-65
references: 17566691
references: Hum Pathol. 2009 Jun;40(6):769-77
references: 19269014
references: Rom J Morphol Embryol. 2007;48(2):121-9
references: 17641798
references: Clin Cancer Res. 2008 Apr 1;14(7):1938-46
references: 18381931
references: Dig Dis Sci. 2006 Aug;51(8):1371-9
references: 16868827
references: J Clin Oncol. 2011 Oct 20;29(30):3968-76
references: 21844504
references: Ann Oncol. 2008 Sep;19(9):1523-9
references: 18441328