FGFR2, HER2 and cMet in gastric adenocarcinoma: Detection, prognostic significance and assessment of downstream pathway activationCitation formats

  • External authors:
  • Guy Betts
  • Helen Valentine
  • Sue Pritchard
  • Richard Swindell
  • Victoria Williams
  • Shethah Morgan
  • Ewen A. Griffiths
  • Ian Welch
  • Christopher Womack

Standard

FGFR2, HER2 and cMet in gastric adenocarcinoma: Detection, prognostic significance and assessment of downstream pathway activation. / Betts, Guy; Valentine, Helen; Pritchard, Sue; Swindell, Richard; Williams, Victoria; Morgan, Shethah; Griffiths, Ewen A.; Welch, Ian; West, Catharine; Womack, Christopher.

In: Virchows Archiv, Vol. 464, No. 2, 02.2014, p. 145-156.

Research output: Contribution to journalArticle

Harvard

Betts, G, Valentine, H, Pritchard, S, Swindell, R, Williams, V, Morgan, S, Griffiths, EA, Welch, I, West, C & Womack, C 2014, 'FGFR2, HER2 and cMet in gastric adenocarcinoma: Detection, prognostic significance and assessment of downstream pathway activation', Virchows Archiv, vol. 464, no. 2, pp. 145-156. https://doi.org/10.1007/s00428-013-1517-y

APA

Betts, G., Valentine, H., Pritchard, S., Swindell, R., Williams, V., Morgan, S., ... Womack, C. (2014). FGFR2, HER2 and cMet in gastric adenocarcinoma: Detection, prognostic significance and assessment of downstream pathway activation. Virchows Archiv, 464(2), 145-156. https://doi.org/10.1007/s00428-013-1517-y

Vancouver

Betts G, Valentine H, Pritchard S, Swindell R, Williams V, Morgan S et al. FGFR2, HER2 and cMet in gastric adenocarcinoma: Detection, prognostic significance and assessment of downstream pathway activation. Virchows Archiv. 2014 Feb;464(2):145-156. https://doi.org/10.1007/s00428-013-1517-y

Author

Betts, Guy ; Valentine, Helen ; Pritchard, Sue ; Swindell, Richard ; Williams, Victoria ; Morgan, Shethah ; Griffiths, Ewen A. ; Welch, Ian ; West, Catharine ; Womack, Christopher. / FGFR2, HER2 and cMet in gastric adenocarcinoma: Detection, prognostic significance and assessment of downstream pathway activation. In: Virchows Archiv. 2014 ; Vol. 464, No. 2. pp. 145-156.

Bibtex

@article{aaea9ab8d39e467fa1588cde01b457db,
title = "FGFR2, HER2 and cMet in gastric adenocarcinoma: Detection, prognostic significance and assessment of downstream pathway activation",
abstract = "Receptor tyrosine kinase pathways are potential therapeutic targets in gastric adenocarcinoma patients. We evaluated HER2 and cMet protein expression, and FGFR2 gene amplification to assess their prognostic significance, and downstream mediators pS6 and pERK for their potential utility as pharmacodynamic biomarkers in patients with gastric adenocarcinoma. Tissue microarrays were constructed from resection samples of 184 patients who underwent surgery for gastric/gastro-oesophageal junction adenocarcinoma. Tissue cores were obtained from the tumour body (TB), luminal surface (LS) and invasive edge (IE), and immunohistochemical and fluorescence in situ hybridisation (FGFR2) analysis was performed. FGFR2 amplification was identified in 2 {\%} of cases and associated with worse survival (P = 0.005). HER2 overexpression was observed in 10 {\%} of cases and associated with increased survival (P = 0.041). cMet overexpression was observed in 4 {\%} of cases and associated with worse survival (P <0.001). On multivariate analysis, only cMet retained significance (P = 0.006). pS6 and pERK expression were observed in 73 {\%} and 30 {\%} of tumours, respectively, with no association with survival. HER2 (P = 0.004) and pERK (P = 0.001) expression differed between tumour regions with HER2 expression increased in the LS compared with the TB and IE. These findings confirm subpopulations in gastric adenocarcinoma with poor outcome that may benefit from specific therapeutic strategies. However, we found heterogeneous HER2, pS6 and pERK overexpression, which presents challenges for their use as predictive biomarkers in gastric biopsies. The potential downstream pharmacodynamic markers pS6 and pERK were expressed across tumour regions, providing evidence that resections and biopsies would yield comparative results in clinical trials. {\circledC} 2013 Springer-Verlag Berlin Heidelberg.",
keywords = "cMet, FGFR2, Gastric adenocarcinoma, HER2, Tissue microarray",
author = "Guy Betts and Helen Valentine and Sue Pritchard and Richard Swindell and Victoria Williams and Shethah Morgan and Griffiths, {Ewen A.} and Ian Welch and Catharine West and Christopher Womack",
year = "2014",
month = "2",
doi = "10.1007/s00428-013-1517-y",
language = "English",
volume = "464",
pages = "145--156",
journal = "Virchows Archiv",
issn = "0945-6317",
publisher = "Springer Nature",
number = "2",

}

RIS

TY - JOUR

T1 - FGFR2, HER2 and cMet in gastric adenocarcinoma: Detection, prognostic significance and assessment of downstream pathway activation

AU - Betts, Guy

AU - Valentine, Helen

AU - Pritchard, Sue

AU - Swindell, Richard

AU - Williams, Victoria

AU - Morgan, Shethah

AU - Griffiths, Ewen A.

AU - Welch, Ian

AU - West, Catharine

AU - Womack, Christopher

PY - 2014/2

Y1 - 2014/2

N2 - Receptor tyrosine kinase pathways are potential therapeutic targets in gastric adenocarcinoma patients. We evaluated HER2 and cMet protein expression, and FGFR2 gene amplification to assess their prognostic significance, and downstream mediators pS6 and pERK for their potential utility as pharmacodynamic biomarkers in patients with gastric adenocarcinoma. Tissue microarrays were constructed from resection samples of 184 patients who underwent surgery for gastric/gastro-oesophageal junction adenocarcinoma. Tissue cores were obtained from the tumour body (TB), luminal surface (LS) and invasive edge (IE), and immunohistochemical and fluorescence in situ hybridisation (FGFR2) analysis was performed. FGFR2 amplification was identified in 2 % of cases and associated with worse survival (P = 0.005). HER2 overexpression was observed in 10 % of cases and associated with increased survival (P = 0.041). cMet overexpression was observed in 4 % of cases and associated with worse survival (P <0.001). On multivariate analysis, only cMet retained significance (P = 0.006). pS6 and pERK expression were observed in 73 % and 30 % of tumours, respectively, with no association with survival. HER2 (P = 0.004) and pERK (P = 0.001) expression differed between tumour regions with HER2 expression increased in the LS compared with the TB and IE. These findings confirm subpopulations in gastric adenocarcinoma with poor outcome that may benefit from specific therapeutic strategies. However, we found heterogeneous HER2, pS6 and pERK overexpression, which presents challenges for their use as predictive biomarkers in gastric biopsies. The potential downstream pharmacodynamic markers pS6 and pERK were expressed across tumour regions, providing evidence that resections and biopsies would yield comparative results in clinical trials. © 2013 Springer-Verlag Berlin Heidelberg.

AB - Receptor tyrosine kinase pathways are potential therapeutic targets in gastric adenocarcinoma patients. We evaluated HER2 and cMet protein expression, and FGFR2 gene amplification to assess their prognostic significance, and downstream mediators pS6 and pERK for their potential utility as pharmacodynamic biomarkers in patients with gastric adenocarcinoma. Tissue microarrays were constructed from resection samples of 184 patients who underwent surgery for gastric/gastro-oesophageal junction adenocarcinoma. Tissue cores were obtained from the tumour body (TB), luminal surface (LS) and invasive edge (IE), and immunohistochemical and fluorescence in situ hybridisation (FGFR2) analysis was performed. FGFR2 amplification was identified in 2 % of cases and associated with worse survival (P = 0.005). HER2 overexpression was observed in 10 % of cases and associated with increased survival (P = 0.041). cMet overexpression was observed in 4 % of cases and associated with worse survival (P <0.001). On multivariate analysis, only cMet retained significance (P = 0.006). pS6 and pERK expression were observed in 73 % and 30 % of tumours, respectively, with no association with survival. HER2 (P = 0.004) and pERK (P = 0.001) expression differed between tumour regions with HER2 expression increased in the LS compared with the TB and IE. These findings confirm subpopulations in gastric adenocarcinoma with poor outcome that may benefit from specific therapeutic strategies. However, we found heterogeneous HER2, pS6 and pERK overexpression, which presents challenges for their use as predictive biomarkers in gastric biopsies. The potential downstream pharmacodynamic markers pS6 and pERK were expressed across tumour regions, providing evidence that resections and biopsies would yield comparative results in clinical trials. © 2013 Springer-Verlag Berlin Heidelberg.

KW - cMet

KW - FGFR2

KW - Gastric adenocarcinoma

KW - HER2

KW - Tissue microarray

U2 - 10.1007/s00428-013-1517-y

DO - 10.1007/s00428-013-1517-y

M3 - Article

VL - 464

SP - 145

EP - 156

JO - Virchows Archiv

JF - Virchows Archiv

SN - 0945-6317

IS - 2

ER -