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FGFR1 Amplification Is Often Homogeneous and Strongly Linked to the Squamous Cell Carcinoma Subtype in Esophageal Carcinoma.
PLoS One. 2015; 10(11):e0141867.Plos

Abstract

BACKGROUND AND AIMS

Amplification of the fibroblast growth factor receptor 1 (FGFR1) is believed to predict response to multi-kinase inhibitors targeting FGFR1. Esophageal cancer is an aggressive disease, for which novel targeted therapies are highly warranted.

METHODS

This study was designed to investigate the prevalence and clinical significance of FGFR1 amplification in a tissue microarray containing 346 adenocarcinomas and 254 squamous cell carcinomas of the esophagus, using dual-labeling fluorescence in situ hybridization (FISH) analysis.

RESULTS

FGFR1 amplification, defined as a ratio of FGFR1:centromere 8 copy numbers ≥ 2.0, was more frequently seen in squamous cell carcinoma (8.9% of 202 interpretable cases) than in adenocarcinoma (1.6% of 308; p<0.0001). There was no association between FGFR1 amplification and tumor phenotype or clinical outcome. To study potential heterogeneity of FGFR1 amplification, all available tumor blocks from 23 FGFR1 amplified tumors were analyzed on conventional large sections. This analysis revealed complete homogeneity of FGFR1 amplification in 20 (86.9%) primary tumors and in all available lymph node metastases. Remarkably, FGFR1 amplification was also seen in dysplasia adjacent to tumor in 6 of 9 patients with FGFR1 amplified primary cancers.

CONCLUSIONS

In conclusion, FGFR1 amplification occurs in a relevant subgroup of carcinomas of the esophagus and may play a particular role for development of squamous cell cancers. The high homogeneity of FGFR1 amplification suggests that patients with FGFR1 amplified esophageal cancers may particularly benefit from anti-FGFR1 therapies and prompt for clinical studies in this tumor type.

Authors+Show Affiliations

Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26555375

Citation

von Loga, Katharina, et al. "FGFR1 Amplification Is Often Homogeneous and Strongly Linked to the Squamous Cell Carcinoma Subtype in Esophageal Carcinoma." PloS One, vol. 10, no. 11, 2015, pp. e0141867.
von Loga K, Kohlhaussen J, Burkhardt L, et al. FGFR1 Amplification Is Often Homogeneous and Strongly Linked to the Squamous Cell Carcinoma Subtype in Esophageal Carcinoma. PLoS ONE. 2015;10(11):e0141867.
von Loga, K., Kohlhaussen, J., Burkhardt, L., Simon, R., Steurer, S., Burdak-Rothkamm, S., Jacobsen, F., Sauter, G., & Krech, T. (2015). FGFR1 Amplification Is Often Homogeneous and Strongly Linked to the Squamous Cell Carcinoma Subtype in Esophageal Carcinoma. PloS One, 10(11), e0141867. https://doi.org/10.1371/journal.pone.0141867
von Loga K, et al. FGFR1 Amplification Is Often Homogeneous and Strongly Linked to the Squamous Cell Carcinoma Subtype in Esophageal Carcinoma. PLoS ONE. 2015;10(11):e0141867. PubMed PMID: 26555375.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - FGFR1 Amplification Is Often Homogeneous and Strongly Linked to the Squamous Cell Carcinoma Subtype in Esophageal Carcinoma. AU - von Loga,Katharina, AU - Kohlhaussen,Jule, AU - Burkhardt,Lia, AU - Simon,Ronald, AU - Steurer,Stefan, AU - Burdak-Rothkamm,Susanne, AU - Jacobsen,Frank, AU - Sauter,Guido, AU - Krech,Till, Y1 - 2015/11/10/ PY - 2015/07/23/received PY - 2015/10/14/accepted PY - 2015/11/12/entrez PY - 2015/11/12/pubmed PY - 2016/6/15/medline SP - e0141867 EP - e0141867 JF - PloS one JO - PLoS ONE VL - 10 IS - 11 N2 - BACKGROUND AND AIMS: Amplification of the fibroblast growth factor receptor 1 (FGFR1) is believed to predict response to multi-kinase inhibitors targeting FGFR1. Esophageal cancer is an aggressive disease, for which novel targeted therapies are highly warranted. METHODS: This study was designed to investigate the prevalence and clinical significance of FGFR1 amplification in a tissue microarray containing 346 adenocarcinomas and 254 squamous cell carcinomas of the esophagus, using dual-labeling fluorescence in situ hybridization (FISH) analysis. RESULTS: FGFR1 amplification, defined as a ratio of FGFR1:centromere 8 copy numbers ≥ 2.0, was more frequently seen in squamous cell carcinoma (8.9% of 202 interpretable cases) than in adenocarcinoma (1.6% of 308; p<0.0001). There was no association between FGFR1 amplification and tumor phenotype or clinical outcome. To study potential heterogeneity of FGFR1 amplification, all available tumor blocks from 23 FGFR1 amplified tumors were analyzed on conventional large sections. This analysis revealed complete homogeneity of FGFR1 amplification in 20 (86.9%) primary tumors and in all available lymph node metastases. Remarkably, FGFR1 amplification was also seen in dysplasia adjacent to tumor in 6 of 9 patients with FGFR1 amplified primary cancers. CONCLUSIONS: In conclusion, FGFR1 amplification occurs in a relevant subgroup of carcinomas of the esophagus and may play a particular role for development of squamous cell cancers. The high homogeneity of FGFR1 amplification suggests that patients with FGFR1 amplified esophageal cancers may particularly benefit from anti-FGFR1 therapies and prompt for clinical studies in this tumor type. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/26555375/FGFR1_Amplification_Is_Often_Homogeneous_and_Strongly_Linked_to_the_Squamous_Cell_Carcinoma_Subtype_in_Esophageal_Carcinoma_ L2 - http://dx.plos.org/10.1371/journal.pone.0141867 DB - PRIME DP - Unbound Medicine ER -