Comparison Between Matched Liquid Biopsy (ctDNA) and FFPE Tumors Molecular Profiles of Lung and Colorectal Cancer Patients in a Molecular Diagnostics Laboratory.

Natalia Rodon1, Yessica No Garbarino1, Montse Verdu1,2, Olga Diaz1, Esther Llaudet1, Juan Moya3, David Coroleu4, M. Antonia Lequerica4, Pedro Barrios4, Joan Borras4, Sandra Mecho5, Ferran Bastart5, Javier Martinez-Agea5 and Xavier Puig1,2,6.

1BIOPAT. Biopatologia Molecular SL. Grup Assistència. Barcelona, Spain. 2HISTOPAT SL. Barcelona, Spain. 3Especialista Cirugía Torácica. Servicio de Cirugía. SCIAS-Hospital de Barcelona, Grup Assistència. Barcelona, Spain. 4Servicio de Cirugía. SCIAS-Hospital de Barcelona, Grup Assistència. Barcelona, Spain. 5Servicio Diagnóstico por la Imagen. SCIAS-Hospital de Barcelona, Grup Assistència. Barcelona, Spain. 6SCIAS-Hospital de Barcelona, Grup Assistència. Barcelona, Spain.


Analysis of circulating tumor DNA (ctDNA), also known as liquid biopsy, has been postulated as a useful test in prognostication, molecular profiling and monitoring of cancer patients. In our laboratory we routinely perform NGS molecular profiling of DNA and RNA extracted from FFPE tumors. In this series we aimed to analyze the performance of a NGS ctDNA assay and explore the level of concordance between the mutation status obtained from previously analyzed FFPE tumor samples and ctDNA.


This retrospective study included cancer patients with a complete morphomolecular diagnostics and gene mutations detected in a previous FFPE tumor NGS study of 22 genes: EGFR, ALK, ERBB2, ERBB4, FGFR1, FGFR2, FGFR3, MET, DDR2, KRAS, PIK3CA, BRAF, AKT1, PTEN, NRAS, MAP2K1, STK11, NOTCH1, CTNNB1, SMAD4, FBXW7 and TP53 (OST DNA. Thermofisher) and with matched frozen plasma sample available for ctDNA study with a NGS assay of 11 genes: ALK, BRAF, EGFR, ERBB2, KRAS, MAP2K1, MET, NRAS, PIK3CA, ROS1 and TP53 (OL cfDNA Assay. Thermofisher). Concordance between ctDNA and tumor were analyzed considering tumor molecular profile as the gold standard technique.   


Series included 30 patients, 17 with colorectal carcinoma (CRC) and 13 with NSCLC. Fifty percent were stage tumor I-II and 50% stage III-IV. ctDNA was successfully extracted from the 30 matched plasma samples with concentrations ranging 0.4 to 2.5ng/μL. Libraries were amplified from 5-33ng of ctDNA. All NGS ctDNA assays reported a valid result with sensitivity ranging from 0.04 to 0.3%. Globally, the concordance rate between FFPE tumors and ctDNA was 53.3%. When tumors were stratified by stage, the concordance was 87.5%, 57.1%, 50% and 14.3% in tumoral stages IV, III, II and I, respectively. These percentages showed the same distribution when CRC and NSCLC were analyzed separately. In 36.7% of ctDNA studies a new mutation not previously detected in the matched tumor was found.


ctDNA NGS assay showed a good performance in the diagnostics molecular laboratory setting. ctDNA molecular profiles showed a good concordance rate in advanced stage tumors and is able to identify undetected mutations in FFPE tumor samples.


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