Day 3 :
Roche Tissue Diagnostics (RTD), USA
Keynote: Rapid Two-Temperature Formalin Tissue Fixation Reduces Assay Variability for Improved Diagnosis and Therapy
Time : 10:00-10:30
David received a B.S. degree in Biochemistry from Purdue University and a PhD in Biochemistry from the University of Iowa. David was both a Cancer Center and NIH postdoctoral fellow at the University of Rochester. David is currently a principal scientist at Roche Tissue Diagnostics located in Tucson Arizona. David is the technical lead for pre-analytics. This project aims to provide standardization of routine tissue collection. Efforts have focused on ways to optimize tissue fixation providing high quality with exceptional turn-around time and higher medical content. David holds several patents on automated immunohistochemistry as well as novel fixation protocols.
Precision medicine is based on obtaining diagnostic and therapeutic data from clinical assays for each individual. In tissue diagnostics, non-standradized pre-analytical factors often confound assay results. One such step, Formalin fixation, is a mainstay of modern histopathologic analysis, yet the practice is poorly standardized and a significant potential source of preanalytical errors. Concerns of workflow and turnaround time drive interest in developing shorter fixation protocols, but rapid protocols can lead to poor histomorphology or inadequate downstream assay results. Variable assay results can lead to errors in diagnosis and treatment depending on the specifics of the disease and biomarkers involved. Additionally, assays such as immunohistochemistry for phosphorylated epitopes have historically been challenging in the context of formalin-fixed tissue, indicating that there may be room for improvement in this process that is fundamental to the practice of anatomic pathology. With these issues in mind, we studied basic formalin biochemistry to develop a novel formalin fixation protocol that involves a pre incubation in subambient temperature formalin prior to a brief exposure to heated formalin(1).
This new protocol is more rapid than standard protocols yet preserves histomorphology and yields tissue that is compatible with an expanded set of downstream clinical and research assays. Using this novel protocol we found increased preservation of phosphorylated epitopes on proteins, important protein biomarkers such as FoxP3 and RNA species such as mRNA and miRNA.
1.Chafin, D., Theiss, A., Roberts, E., Borlee, G., Otter, M., and Baird, G. S. (2013) Rapid two-temperature formalin fixation. PLoS One 8, e54138
University of Pittsburgh School of Medicine, USA
Keynote: Genome biomarkers of prostate cancer
Time : 10:30-11:00
Luo is a member of the Divisions of Experimental Pathology, Molecular and Cellular Pathology and Anatomic Molecular Pathology. He is the Director of the High Throughput Genome Center at the Department of Pathology, University of Pittsburgh, involving collaboration of faculties from multiple departments.
Dr. Luo been studying molecular pathology related to human malignancies in the last 23 years. Currently, he is a Professor of Pathology and Director of High Throughput Genome Center at University of Pittsburgh. In the last 13 years, Dr. Luo has been largely focusing on genetic and molecular mechanism of human prostate and hepatocellular carcinomas.
Accurate prediction of prostate cancer clinical courses remains elusive. In recent studies, we performed whole genome analysis on prostate cancers by combining Affymetrix SNP6.0 chip, whole genome sequencing and transcriptome sequencing. Our results showed that combination of genome copy number variance and novel fusion transcripts specific for cancer achieved high accuracy in predicting prostate cancer outcomes. The prediction model was further improved when these molecular criteria were combined with Nomogram or Gleason’s grading, leukocyte CNV. Interestingly, some of these fusion genes are also present in a variety of human malignancies. Some of these fusion genes play critical roles in developing malignancies. Critical signaling pathways associated with some of these fusion genes have been characterized. Targeting at fusion gene appears to be an effective approach in killing cancer cells both in vitro and in vivo, and holds promise as a new treatment for human malignancies.
The Johns Hopkins Medical Institutions, USA
Keynote: Biomarkers in the accurate classification of Non-Small Cell Lung Carcinomas (NSCLC) for targeted therapies: An evidence-based practice
Time : 11:20-11:50
Qing Kay Li is an associate professor of pathology at the Johns Hopkins University School of Medicine. She has the American Board of Pathology certification in anatomic and clinical pathology, and subspecialty certification in cytopathology. Her areas of clinical expertise include surgical pathology and cytopathology.
Dr. Li is also a faculty member and co-PI at the Johns Hopkins Biomarker Discovery Center. Her research interests are focusing on the application of advanced cellular and molecular techniques to the field of cytopathology and cancer biology, particularly in the field of early detection of lung and prostate cancer.
The current recommendations of IASLC (International Association for the Study of Lung Cancer) and the WHO classification (2015 edition) emphasize the use of minimal tumor tissue for morphological diagnosis and for immunohistochemical (IHC) stains. Accurate classification of NSCLC into adenocarcinoma (ADC) and/or squamous cell carcinoma (SqCC) plays a crucial role in molecular targeted therapies and clinical management of lung cancer patients. The morphological heterogeneity and updated classification criteria of lung cancer present diagnostic challenges in using small biopsy specimens. The distinction between ADC and SqCC may be difficult in small fine needle aspiration (FNA) biopsy specimens. Here, we will discuss the sensitivity and specificity of commonly used IHC biomarkers, including TTF-1, Napsin A, CK7, P63, P40 and CK5/6 in the classification of NSCLC. Furthermore, the combination of several individual IHC markers into a novel triple biomarker is increasingly used in daily practice. We will also discuss our data of this novel triple biomarker in the sub-classification of NSCLC, including its limitation and diagnostic pitfall. The optimal goal of current practice is preservation of tumor tissue for molecular analysis, and to provide the guidance for molecular targeted therapy.