Quality Control for Biomarker Determination in Oncology: The Experience of the Italian Network for Quality Assessment of Tumor Biomarkers (INQAT)

Abstract

Biomarker analysis and evaluation in oncology is the product of a number of processes (including managerial, technical and interpretation steps) which need to be monitored and controlled to prevent and correct errors and guarantee a satisfactory level of quality. Several biomarkers have recently moved to clinical validation studies and successively to clinical practice without any definition of standard procedures and/or quality control (QC) schemes necessary to guarantee the reproducibility of the laboratory information. In Italy several national scientific societies and single researchers have activated -- often on a pilot level -- specific external quality assessment protocols, thereby potentially jeopardizing the clinical reality even further. In view of the seriousness of the problem, in 1998 the Italian Ministry of Health sponsored a National Survey Project to coordinate and standardize the procedures and to develop QC programs for the analysis of cancer biomarkers of potential clinical relevance. Twelve QC programs focused on biomarkers and concerning morphological, immunohistochemical, biochemical, molecular, and immunoenzymatic assays were coordinated and implemented. Specifically, external QC programs for the analytical phase of immunohistochemical p53, Bcl-2, c-erb-2/neu/HER2, and microvessel density determination, of morphological evaluation of tumor differentiation grade, and of molecular p53 analysis were activated for the first time within the project. Several hundreds of Italian laboratories took part in these QC programs, the results of which are available on the web site of the Network (www.cqlaboncologico.it). Financial support from the Italian Government and the National Research Council (CNR) will guarantee the pursuit of activities that will be extended to new biomarkers, to preanalytical phases of the assays, and to revision of the criteria of clinical usefulness for evaluating the cost/benefit ratio.

p53, cathepsin D, Bcl-2 are joint prognostic indicators of breast cancer metastatic spreading

“…cathepsin D, uPA, MMP-11, are secreted by transformed or stromal cells of BC, and impact on tumor invasion and mestastasis [ 66 – 76 ]. uPA is modulated by the plasminogen activator inhibitor-1 (PAI-1), and combined assessment of uPA and PAI-1 was shown to be of value for prognostic determination [ 77 , 78 ], indicating an impact of overall proteolytic balance on tumor progression. As indicated above for loss of Bcl-2, triple-negative BC were frequently associated with overexpression of cathepsin-D, and with aggressive disease course through lymph node invasion and high cancer cell proliferation/Ki-67 index [ 79 ].…”

Phase III randomized multicenter study on the effects of adjuvant CMF in patients with node-negative, rapidly proliferating breast cancer: twelve-year results and retrospective subgroup analysis

“…Intra-and interlaboratory quality controls were periodically repeated within the context of a National Quality Control Programme, activated for TLI in the late 1980s [11], and maintained as part of the National Oncology Project promoted by the National Research Council (CNR) and the Ministry of Education, University and Research (MIUR) [12].…”

Biostatistics and Tumor Marker Studies in Breast Cancer: Design, Analysis and Interpretation Issues

“…Statistical methods play a key role in assay development and validation of the analytical performance of quantitative biochemical assays and qualitative pathological examination. In addition, quality control guidelines must be implemented for routine measurements, including internal quality control to confirm the stability of the precision and accuracy specifications that were determined in the validation phase, and external quality control, to assess the relative and absolute accuracy of assays in different laboratories by measuring the same reference samples (7).…”