Toussaint J, Sieuwerts AM, Haibe-Kains B, Desmedt C, Rouas G, Harris AL, Larsimont D, Piccart M, Foekens JA, Durbecq V, Sotiriou C
Improvement of the clinical applicability of the Genomic Grade Index through a qRT-PCR test performed on frozen and formalin-fixed paraffin-embedded tissues. [JOURNAL ARTICLE]
BMC Genomics 2009 Sep 10; 10(1):424.
ABSTRACT:
BACKGROUND: Proliferation and tumor differentiation captured by the genomic grade index (GGI) are important prognostic indicators in breast cancer (BC) especially for the estrogen receptor positive (ER+) disease. The aims of this study were to convert this microarray index to a qRT-PCR assay (PCR-GGI), which could be realized on formalin fixed paraffin embedded samples (FFPE), and to assess its prognostic performance and predictive value of clinical benefit in early and advanced ER+ BC patients treated with tamoxifen.
METHODS: The accuracy and concordance of the PCR-GGI with the GGI was assessed using BC patients for which frozen and FFPE tissues as well as microarray data were available (n=19). The evaluation of the prognostic value of the PCR-GGI was assessed on FFPE material using a consecutive series of 212 systemically treated early BC patients. The predictive performance for tamoxifen benefit was assessed using two ER+ BC populations treated either with adjuvant tamoxifen only (n=77+139) or first-line tamoxifen for advanced disease (n=270).
RESULTS: The PCR-GGI is based on the expression of 8 genes (4 representative of the GGI genes and 4 reference genes). A significant correlation was observed between the microarray-derived GGI and the qRT-PCR assay using frozen (rho=0.95, p<10E-06) and FFPE material (rho=0.89, p<10E-06). The prognostic performance of the PCR-GGI was confirmed on FFPE samples (HRunivar.=1.89; [95CI:1.01-3.54], p=0.05). The PCR-GGI further identified two subgroups of patients with statistically different time to distant metastasis free survival (DMFS) across the two cohorts of ER+ BC patients treated with adjuvant tamoxifen. Additionally, the PCR-GGI was associated with response to tamoxifen in the advanced setting (HRunivar.=1.98; [95CI:1.51-2.59], p=6.9E-07).
CONCLUSIONS: PCR-GGI recapitulates in an accurate and reproducible manner the performances of the GGI using frozen and FFPE samples.
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