ABSTRACT
Circulating tumor DNA (ctDNA) has shown great potential in targeted therapy efficacy prediction, monitoring, high-risk population screening, differential diagnosis, minimal residual disease (MRD) monitoring, and prognosis prediction. The detection of specific gene mutations in ctDNA had been included in clinical practice guidelines for certain tumors to predict the drug efficacy and monitor resistance. A small number of approved companion diagnostic reagents have been used in clinical setting. However, the clinical validity of most ctDNA-related biomarkers it still in the research stage. Besides, the establishment and validation of laboratory-developed tests (LDT) are also problems that need to be solved urgently. Therefore, for the moment, the clinical application of ctDNA analysis is like two sides of a coin, with both opportunities and challenges.
ABSTRACT
Objective To evaluate the performance of KRAS gene mutation detection in 2014 external quality assessment ( EQA ) program and discuss the problems in clinical laboratories .Methods The sample panel of 2014 EQA program contained 5 artificial formalin-fixed, paraffin-embedded ( FFPE) samples.The participating laboratories were asked to report their results before the deadline .The scores of EQA and the rate of overall coincidence , false positive and false negative were calculated .Results The EQA program for KRAS testing was set twice a year .In 2014, 58 and 57 valid lab results were submitted respectively.About 79.31%(46/58)and 94.73%(54/57) of the laboratories were correct for all samples. The coincidence rate of positive samples were 93.53% ( 217/232 ) and 96.49% ( 165/171 ) . The coincidence rate for negative ones were 100%(58/58) and 98.25% (112/114).The false-negative ratio was 1.29%( 3/232 ) and 0%.The false-positive ratio was 4.14% ( 12/290 ) and 3.15% ( 9/285 ) . Conclusions The results of 2014 EQA for KRAS gene mutation testing suggested that the performance of laboratories had been improved significantly , however , the false-negative and false-positive results had always been the major problems affecting the accuracy of KRAS mutations testing .Laboratories needed to standardize the testing process and manufacturers should optimize the reagents and the way of interpretation , to guarantee the performance of KRAS gene mutation detection .