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FGFR2 in gastric cancer: protein overexpression predicts gene amplification and high H-index predicts poor survival.

Publication ,  Journal Article
Ahn, S; Lee, J; Hong, M; Kim, ST; Park, SH; Choi, MG; Lee, J-H; Sohn, TS; Bae, JM; Kim, S; Jung, S-H; Kang, WK; Kim, K-M
Published in: Mod Pathol
September 2016

FGFR2 gene amplification, and resulting FGFR2 protein overexpression, is rare in gastric cancer patients, and development of an accurate and widely available method for mass screening to identify patients who may respond to treatment with fibroblast growth factor receptor (FGFR) inhibitors is important. We first screened 312 gastric cancer patients with known copy number variations by FGFR2b immunohistochemistry using FPR2-D, an isoform-specific antibody. Next, we performed immunohistochemistry on tissue microarrays from 1574 gastric cancer patients. Selected cases were analyzed for FGFR2 amplification by FISH. In addition, FGFR2b overexpression was studied in 88 matched primary and metastatic gastric cancers. In the first cohort, FGFR2b immunohistochemistry results correlated very well with those of copy number variation (r=0.79) and FISH (r=1.0). In total, FGFR2b overexpression was identified in 73 of 1974 gastric cancers (4%). The concordance between immunohistochemistry and FISH was extremely high; all 2+ and 3+ cases identified by immunohistochemistry were FGFR2 amplified. In the matched primary and metastatic gastric cancer pairs, the positivity and percentage of positive tumor cells were significantly higher in metastatic gastric cancers than in primary gastric cancers (8% vs 3% and 75% vs 47%, respectively; P<0.001). FGFR2b overexpression was significantly more frequent in gastric cancers with diffuse subtype (P=0.01) and higher N stage (P=0.006). FGFR2b overexpression with H-score ≥150 were independent prognostic factors for overall survival with hazard ratio of 1.836 (95% confidence interval, 1.034-3.261; P=0.038). FGFR2b positivity in immunohistochemistry was strongly correlated with FGFR2 amplification. Given the low frequency of FGFR2 amplification in gastric cancers, FGFRb2 immunohistochemistry is an accurate screening tool to detect FGFR2 amplification, and both primary and metastatic gastric cancer tissues should be tested to select gastric cancer patients for treatment with FGFR2 inhibitors.

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Published In

Mod Pathol

DOI

EISSN

1530-0285

Publication Date

September 2016

Volume

29

Issue

9

Start / End Page

1095 / 1103

Location

United States

Related Subject Headings

  • Up-Regulation
  • Tissue Array Analysis
  • Stomach Neoplasms
  • Receptor, Fibroblast Growth Factor, Type 2
  • Proportional Hazards Models
  • Phenotype
  • Pathology
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate
 

Citation

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Ahn, S., Lee, J., Hong, M., Kim, S. T., Park, S. H., Choi, M. G., … Kim, K.-M. (2016). FGFR2 in gastric cancer: protein overexpression predicts gene amplification and high H-index predicts poor survival. Mod Pathol, 29(9), 1095–1103. https://doi.org/10.1038/modpathol.2016.96
Ahn, Soomin, Jeeyun Lee, Mineui Hong, Seung Tae Kim, Se Hoon Park, Min Gew Choi, Jun-Ho Lee, et al. “FGFR2 in gastric cancer: protein overexpression predicts gene amplification and high H-index predicts poor survival.Mod Pathol 29, no. 9 (September 2016): 1095–1103. https://doi.org/10.1038/modpathol.2016.96.
Ahn S, Lee J, Hong M, Kim ST, Park SH, Choi MG, et al. FGFR2 in gastric cancer: protein overexpression predicts gene amplification and high H-index predicts poor survival. Mod Pathol. 2016 Sep;29(9):1095–103.
Ahn, Soomin, et al. “FGFR2 in gastric cancer: protein overexpression predicts gene amplification and high H-index predicts poor survival.Mod Pathol, vol. 29, no. 9, Sept. 2016, pp. 1095–103. Pubmed, doi:10.1038/modpathol.2016.96.
Ahn S, Lee J, Hong M, Kim ST, Park SH, Choi MG, Lee J-H, Sohn TS, Bae JM, Kim S, Jung S-H, Kang WK, Kim K-M. FGFR2 in gastric cancer: protein overexpression predicts gene amplification and high H-index predicts poor survival. Mod Pathol. 2016 Sep;29(9):1095–1103.

Published In

Mod Pathol

DOI

EISSN

1530-0285

Publication Date

September 2016

Volume

29

Issue

9

Start / End Page

1095 / 1103

Location

United States

Related Subject Headings

  • Up-Regulation
  • Tissue Array Analysis
  • Stomach Neoplasms
  • Receptor, Fibroblast Growth Factor, Type 2
  • Proportional Hazards Models
  • Phenotype
  • Pathology
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate