Electron microscopy is a powerful tool used to assist in the diagnosis of complex pathological diseases where there is a benefit from the analysis of the fine structures of a biopsy. These include, but are not limited to, kidney, nerve, skin and ciliary biopsies.
Washington University Diagnostic Laboratory Services provides state-of-the-art CAP/CLIA certified laboratory services ranging from classical techniques such as electron microscopy to the latest molecular techniques including next-generation sequencing and chromosomal microarray.
Areas of technical expertise
Histology, immunohistochemistry and in-situ hybridization
Classical cytogenetic analysis of karyotyping is utilized to identify numerical and structural abnormalities at the level of the chromosome. Routine karyotype analysis is most often performed by GTG-banding, however our lab is capable of analysis using C or NOR banding. All samples are cultured according to the type of specimen and the requirements for compete analysis. Our laboratory performs karyotype analysis for any clinical need, including congenital and acquired disorders.
Karyotype analysis utilized in the diagnosis of congenital disorders can be performed on a number of specimen types including amniotic fluid, chorionic villi, products of conception and peripheral blood.
Chromosome analysis for the diagnosis and monitoring of acquired disorders can be performed on several specimen types such as bone marrow, bone core biopsy, involved blood and solid tumor tissue samples.
Chromosomal microarray analysis (CMA)
Chromosomal microarray analysis (CMA) is a high resolution molecular genetic test which is able to detect very small gains and losses across the entire genome. Our CMA has more than 2.67 million unique markers which report copy-number, 750,000 of which are SNP probes and over 1.9 million non-polymorphic copy number probes. Copy-number probes can provide information for deletion, duplication, marker chromosomes and other unbalanced rearrangements. The SNP probes can identify long contiguous stretches of homozygosity (LSCH) which can contribute to disease.
CMA testing is performed for a wide range of constitutional disorders, prenatal testing and products of conception. Common constitutional indications are developmental delay, neurologic abnormalities, multiple congenital anomalies, dysmorphic features and cardiac abnormalities. Prenatal CMA is performed for structural fetal anomalies, early onset IUGR, thickened nuchal translucency, abnormal serum screening and advanced maternal age.
Fluorescence in-situ hybridization (FISH)
Fluorescence in situ hybridization (FISH) testing is a molecular cytogenetic method that identifies specific structural rearrangements or aneuplodies in interphase nuclei or metaphase chromosomes using fluorescently labeled probes. Molecular cytogenetic analysis via FISH is utilized to establish the diagnosis, determine the classification, and monitor the treatment of a vast number of congenital and acquired chromosome abnormalities.
FISH analysis for some cancers (leukemias, lymphomas and other hematological malignancies) and rapid diagnosis of aneuploidy is typically provided within 24 to 48 hours from receipt of the specimen.
Next-generation sequencing allows for the analysis of multiple genetic loci in a single test, conserving valuable surgical specimens and resulting in efficient cost and turnaround times.
Testing multiple genes and sequencing the entire coding regions also allows for the most comprehensive analysis and can identify recurrent and novel variants. In addition, our hybridization capture-based NGS can detect mutations at low allele fraction, from small samples that yield only nanogram amounts of DNA.
Genetic testing in oncology provides information useful for diagnosis, prognosis (disease stratification) and treatment selection. Indeed, a single mutation may impact all of these areas.
The vast majority of this clinically relevant information applies to the effects of isolated mutations, and the current challenge is to understand how recurrent isolated mutations behave in different combinations.
A much greater challenge is to discover important cryptic oncogenic mutations and to learn how they interact with other non-oncogenic alleles and polymorphisms that modify the cancer phenotype.
In constitutional disease, next-generation sequencing can be equally useful.
Many times, patients present with a variety of related phenotypes making diagnosis challenging. Targeted next-generation sequencing provides clinicians with a powerful tool to analyze multiple genes with clinical relevance to enhance the diagnostic yield of testing.
Identification of a pathogenic mutation can often be used to make a more definitive diagnosis, allowing for more appropriate patient management. It also enables tailored genetic counseling in both the patient and at-risk family members.
Over time, such analyses have the potential for genotype-phenotype correlations to be drawn and may enable disease-specific therapies.
Learn more about the CAP/CLIA laboratories that support all of our pathology services.