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Breast Cancer Research
Published in: Breast Cancer Research 2/2007

Open Access 01-12-2007 | Research article

FGFR1 amplification in breast carcinomas: a chromogenic in situhybridisation analysis

Authors: Somaia Elbauomy Elsheikh, Andrew R Green, Maryou BK Lambros, Nicholas C Turner, Matthew J Grainge, Des Powe, Ian O Ellis, Jorge S Reis-Filho

Published in: Breast Cancer Research | Issue 2/2007

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Abstract

Background

The amplicon on 8p11.2 is reported to be found in up to 10% of breast carcinomas. It has been demonstrated recently that this amplicon has four separate cores. The second core encompasses important oncogene candidates, including the fibroblast growth factor receptor 1 (FGFR1) gene. Recent studies have demonstrated that specific FGFR1 amplification correlates with gene expression and that FGFR1 activity is required for the survival of a FGFR1 amplified breast cancer cell line.

Methods

FGFR1 amplification was analysed in tissue microarrays comprising a cohort of 880 unselected breast tumours by means of chromogenic in situ hybridisation using inhouse-generated FGFR1-specific probes. Chromogenic in situ hybridisation signals were counted in a minimum 30 morphologically unequivocal neoplastic cells. Amplification was defined as >5 signals per nucleus in more than 50% of cancer cells or when large gene copy clusters were seen.

Results

FGFR1 amplification was observed in 8.7% of the tumours and was significantly more prevalent in patients >50 years of age and in tumours that lacked HER2 expression. No association was found with other histological parameters. Survival analysis revealed FGFR1 amplification as an independent prognostic factor for overall survival in the whole cohort. Subgroup analysis demonstrated that the independent prognostic impact of FGFR1 amplification was only seen in patients with oestrogen-receptor-positive tumours, where FGFR1 amplification was the strongest independent predictor of poor outcome.

Conclusion

Given that up to 8.7% of all breast cancers harbour FGFR1 amplification and that this amplification is an independent predictor of overall survival, further studies analysing the FGFR1 as a potential therapeutic target for breast cancer patients are warranted.
Appendix
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Literature
1.
Courjal F, Cuny M, Simony-Lafontaine J, Louason G, Speiser P, Zeillinger R, Rodriguez C, Theillet C: Mapping of DNA amplifications at 15 chromosomal localizations in 1875 breast tumors: definition of phenotypic groups. Cancer Res. 1997, 57: 4360-4367.PubMed
2.
Cuny M, Kramar A, Courjal F, Johannsdottir V, Iacopetta B, Fontaine H, Grenier J, Culine S, Theillet C: Relating genotype and phenotype in breast cancer: an analysis of the prognostic significance of amplification at eight different genes or loci and of p53 mutations. Cancer Res. 2000, 60: 1077-1083.PubMed
3.
Gelsi-Boyer V, Orsetti B, Cervera N, Finetti P, Sircoulomb F, Rouge C, Lasorsa L, Letessier A, Ginestier C, Monville F, et al: Comprehensive profiling of 8p11-12 amplification in breast cancer. Mol Cancer Res. 2005, 3: 655-667. 10.1158/1541-7786.MCR-05-0128.CrossRefPubMed
4.
Prentice LM, Shadeo A, Lestou VS, Miller MA, deLeeuw RJ, Makretsov N, Turbin D, Brown LA, Macpherson N, Yorida E, et al: NRG1 gene rearrangements in clinical breast cancer: identification of an adjacent novel amplicon associated with poor prognosis. Oncogene. 2005, 24: 7281-7289. 10.1038/sj.onc.1208892.CrossRefPubMed
5.
Theillet C, Adelaide J, Louason G, Bonnet-Dorion F, Jacquemier J, Adnane J, Longy M, Katsaros D, Sismondi P, Gaudray P, et al: FGFRI and PLAT genes and DNA amplification at 8p12 in breast and ovarian cancers. Genes Chromosomes Cancer. 1993, 7: 219-226. 10.1002/gcc.2870070407.CrossRefPubMed
6.
Ugolini F, Adelaide J, Charafe-Jauffret E, Nguyen C, Jacquemier J, Jordan B, Birnbaum D, Pebusque MJ: Differential expression assay of chromosome arm 8p genes identifies frizzled-related (FRP1/FRZB) and fibroblast growth factor receptor 1 (FGFR1) as candidate breast cancer genes. Oncogene. 1999, 18: 1903-1910. 10.1038/sj.onc.1202739.CrossRefPubMed
7.
Garcia MJ, Pole JC, Chin SF, Teschendorff A, Naderi A, Ozdag H, Vias M, Kranjac T, Subkhankulova T, Paish C, et al: A 1 Mb minimal amplicon at 8p11-12 in breast cancer identifies new candidate oncogenes. Oncogene. 2005, 24: 5235-5245. 10.1038/sj.onc.1208741.CrossRefPubMed
8.
Ray ME, Yang ZQ, Albertson D, Kleer CG, Washburn JG, Macoska JA, Ethier SP: Genomic and expression analysis of the 8p11-12 amplicon in human breast cancer cell lines. Cancer Res. 2004, 64: 40-47. 10.1158/0008-5472.CAN-03-1022.CrossRefPubMed
9.
Yang ZQ, Albertson D, Ethier SP: Genomic organization of the 8p11-p12 amplicon in three breast cancer cell lines. Cancer Genet Cytogenet. 2004, 155: 57-62. 10.1016/j.cancergencyto.2004.03.013.CrossRefPubMed
10.
Eswarakumar VP, Lax I, Schlessinger J: Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005, 16: 139-149. 10.1016/j.cytogfr.2005.01.001.CrossRefPubMed
11.
Welm BE, Freeman KW, Chen M, Contreras A, Spencer DM, Rosen JM: Inducible dimerization of FGFR1: development of a mouse model to analyze progressive transformation of the mammary gland. J Cell Biol. 2002, 157: 703-714. 10.1083/jcb.200107119.CrossRefPubMedPubMedCentral
12.
Xian W, Schwertfeger KL, Vargo-Gogola T, Rosen JM: Pleiotropic effects of FGFR1 on cell proliferation, survival, and migration in a 3D mammary epithelial cell model. J Cell Biol. 2005, 171: 663-673. 10.1083/jcb.200505098.CrossRefPubMedPubMedCentral
13.
Suyama K, Shapiro I, Guttman M, Hazan RB: A signaling pathway leading to metastasis is controlled by N-cadherin and the FGF receptor. Cancer Cell. 2002, 2: 301-314. 10.1016/S1535-6108(02)00150-2.CrossRefPubMed
14.
Reis-Filho JS, Simpson PT, Turner NC, Lambros MB, Jones C, Mackay A, Grigoriadis A, Sarrio D, Savage K, Dexter T, et al: FGFR1 emerges as a potential therapeutic target for lobular breast carcinomas. Clin Cancer Res. 2006, 12: 6652-6662. 10.1158/1078-0432.CCR-06-1164.CrossRefPubMed
15.
Letessier A, Sircoulomb F, Ginestier C, Cervera N, Monville F, Gelsi-Boyer V, Esterni B, Geneix J, Finetti P, Zemmour C, et al: Frequency, prognostic impact, and subtype association of 8p12, 8q24, 11q13, 12p13, 17q12, and 20q13 amplifications in breast cancers. BMC Cancer. 2006, 6: 245-10.1186/1471-2407-6-245.CrossRefPubMedPubMedCentral
16.
Reis-Filho JS, Pinheiro C, Lambros MB, Milanezi F, Carvalho S, Savage K, Simpson PT, Jones C, Swift S, Mackay A, et al: EGFR amplification and lack of activating mutations in metaplastic breast carcinomas. J Pathol. 2006, 209: 445-453. 10.1002/path.2004.CrossRefPubMed
17.
Reis-Filho JS, Savage K, Lambros MB, James M, Steele D, Jones RL, Dowsett M: Cyclin D1 protein overexpression and CCND1 amplification in breast carcinomas: an immunohistochemical and chromogenic in situ hybridisation analysis. Mod Pathol. 2006, 19: 999-1009. 10.1038/modpathol.3800621.CrossRefPubMed
18.
Lambros MB, Simpson PT, Jones C, Natrajan R, Westbury C, Steele D, Savage K, Mackay A, Schmitt FC, Ashworth A, et al: Unlocking pathology archives for molecular genetic studies: a reliable method to generate probes for chromogenic and fluorescent in situ hybridization. Lab Invest. 2006, 86: 398-408. 10.1038/labinvest.3700390.CrossRefPubMed
19.
Tanner M, Gancberg D, Di Leo A, Larsimont D, Rouas G, Piccart MJ, Isola J: Chromogenic in situ hybridization: a practical alternative for fluorescence in situ hybridization to detect HER-2/neu oncogene amplification in archival breast cancer samples. Am J Pathol. 2000, 157: 1467-1472.CrossRefPubMedPubMedCentral
20.
Isola J, Tanner M: Chromogenic in situ hybridization in tumor pathology. Methods Mol Med. 2004, 97: 133-144.PubMed
21.
Isola J, Tanner M, Forsyth A, Cooke TG, Watters AD, Bartlett JM: Interlaboratory comparison of HER-2 oncogene amplification as detected by chromogenic and fluorescence in situ hybridization. Clin Cancer Res. 2004, 10: 4793-4798. 10.1158/1078-0432.CCR-0428-03.CrossRefPubMed
22.
Madjd Z, Pinder SE, Paish C, Ellis IO, Carmichael J, Durrant LG: Loss of CD59 expression in breast tumours correlates with poor survival. J Pathol. 2003, 200: 633-639. 10.1002/path.1357.CrossRefPubMed
23.
Elston CW, Ellis IO: Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991, 19: 403-410. 10.1111/j.1365-2559.1991.tb00229.x.CrossRefPubMed
24.
Singletary SE, Connolly JL: Breast cancer staging: working with the sixth edition of the AJCC Cancer Staging Manual. CA Cancer J Clin. 2006, 56: 37-47.CrossRefPubMed
25.
Galea MH, Blamey RW, Elston CE, Ellis IO: The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat. 1992, 22: 207-219. 10.1007/BF01840834.CrossRefPubMed
26.
Abd El-Rehim DM, Ball G, Pinder SE, Rakha EA, Paish C, Robertson JFR, MacMillan D, Blamey RW, Ellis IO: High throughput protein expression analysis using tissue microarray technology of a large well characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int J Cancer. 2005, 116: 340-350. 10.1002/ijc.21004.CrossRefPubMed
27.
Abd El-Rehim DM, Pinder SE, Paish CE, Bell J, Blamey RW, Robertson JF, Nicholson RI, Ellis IO: Expression of luminal and basal cytokeratins in human breast carcinoma. J Pathol. 2004, 203: 661-671. 10.1002/path.1559.CrossRefPubMed
28.
Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, et al: Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004, 10: 5367-5374. 10.1158/1078-0432.CCR-04-0220.CrossRefPubMed
29.
Bautista S, Theillet C: CCND1 and FGFR1 coamplification results in the colocalization of 11q13 and 8p12 sequences in breast tumor nuclei. Genes Chromosomes Cancer. 1998, 22: 268-277. 10.1002/(SICI)1098-2264(199808)22:4<268::AID-GCC2>3.0.CO;2-T.CrossRefPubMed
30.
McLeskey SW, Ding IY, Lippman ME, Kern FG: MDA-MB-134 breast carcinoma cells overexpress fibroblast growth factor (FGF) receptors and are growth-inhibited by FGF ligands. Cancer Res. 1994, 54: 523-530.PubMed
31.
Coumoul X, Deng CX: Roles of FGF receptors in mammalian development and congenital diseases. Birth Defects Res C Embryo Today. 2003, 69: 286-304. 10.1002/bdrc.10025.CrossRefPubMed
32.
Roumiantsev S, Krause DS, Neumann CA, Dimitri CA, Asiedu F, Cross NC, Van Etten RA: Distinct stem cell myeloproliferative/T lymphoma syndromes induced by ZNF198-FGFR1 and BCR-FGFR1 fusion genes from 8p11 translocations. Cancer Cell. 2004, 5: 287-298. 10.1016/S1535-6108(04)00053-4.CrossRefPubMed
33.
Chen J, Deangelo DJ, Kutok JL, Williams IR, Lee BH, Wadleigh M, Duclos N, Cohen S, Adelsperger J, Okabe R, et al: PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder. Proc Natl Acad Sci USA. 2004, 101: 14479-14484. 10.1073/pnas.0404438101.CrossRefPubMedPubMedCentral
Metadata
Title
FGFR1 amplification in breast carcinomas: a chromogenic in situhybridisation analysis
Authors
Somaia Elbauomy Elsheikh
Andrew R Green
Maryou BK Lambros
Nicholas C Turner
Matthew J Grainge
Des Powe
Ian O Ellis
Jorge S Reis-Filho
Publication date
01-12-2007
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 2/2007
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1665

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