Molecular pathology and cytogenetic testing are becoming more prevalent in both the current diagnosis and the determination of future diagnosis of disease in individuals. We are hearing more frequently about high profile people who are doing preventative surgery and treatments based on their likelihood of developing a particular disease in the future.
These tests are paving the way for determining at-risk populations, probabilities for contraction and general timeframes for developing a disease. The theory is that with quicker diagnosis and more successful treatment of individuals based on their particular genetic profiles, there will be a better outcome for that patient. In addition to a host of prenatal and neonatal screenings for abnormalities, the diagnosis of several leukemias, lymphomas, and certain kinds of solid tumors depend heavily on cytogenetic analysis of specific chromosomal aberrations observed in these cancers.
Using a combination of well-known and leading edge techniques, laboratories are conducting molecular and cytogenetic tests for physicians and patients directly. Armed with this information concerning an individual’s personal genetic makeup, physicians and patients themselves can guide treatment using the most successful recommended courses of action for similar cases.
Several standard types of tests are performed to identify the presence of and future probability for developing, disease. A high level overview is as follows:
- Karyotyping – the routine analysis of metaphase chromosomes that have been banded with trypsin followed by Giemsa, Leishmanns, or a mixture of both creating unique banding patterns on the chromosomes.
- Fluorescent In Situ Hybridization (FISH)- a powerful cytogenetic method used to detect the presence or absence of RNA or DNA sequences in cells, tissues and tumors by tagging gene portions with a labeled probe. Actual reading of the data is conducted using fluorescence microscopy, allowing for the determination of where the fluorescent probe is bound to the DNA fragment.
- SKY (Spectral Karyotyping) and M-FISH (Multiplex FISH) – SKY and M-FISH are molecular cytogenetic techniques that permit the visualization of every chromosome in unique colors, which in turn enables karyotype analysis.
- Comparative Genomic Hybridization (CGH) – a fluorescent molecular cytogenetic technique that identifies DNA gains, losses, and amplifications that maps these variations to normal metaphase chromosomes. It provides a significant advantage for screening chromosomal number changes in tumor genomes and affords the ability to analyze entire genomes with one experiment. CGH has the advantage of requiring only genomic tumor DNA, making it highly useful in laboratories that focus on cancer cytogenetics.
The IT Connection
How does this relate to the IT infrastructure and features of the laboratory information system? By automating your laboratory to include an LIS that is able to support full bi-directional interfaces with your instrumentation, you are able to view the results, incorporate the slides, images and data directly from the instrument to the case within the LIS. You can be viewing the high-definition image for reading on screen while either dictating or typing directly into the observation or notes area within your case. The workflow for this type of testing relies heavily upon being eyes-on and hands-free or with having minimal keystrokes for relieving the burden of going back and forth between screens, instruments, etc., which increases the opportunity for error and fatigue.
Cytogenetics analyzes the number and structure of human and animal chromosomes as well as changes that impact the number and structure of the chromosomes that can cause problems with growth, development, and function. Chromosomal abnormalities can occur at multiple times throughout the life of an organism – when egg and sperm cells are being made, during early fetal development, or after birth. Changes to chromosome structure can disrupt genes, which impacts the proteins causing them to be missing or defective. Depending on when these changes happen, and where, in chromosomes leads to birth defects, syndromes or cancer.
One of the most common instances of cytogenetic analyses is during pregnancy to determine if a fetus is at risk for common syndromes caused by having extra or missing chromosomes, syndromes caused by structural defects in chromosomes, or to determine if extra or missing genetic material is detected.
The same cytogenetic analyses can be performed on a newborn or a child with multiple anomalies or developmental delays to look for a potential chromosomal abnormality. With the information provided by cytogenetic analyses, accurate diagnoses can be made so that early and effective treatment can lead to better outcomes.
In many instances, cytogenetic testing is done before pregnancy and can aid in decision making during reproductive discussions.
The analysis of chromosomes in human development and disease is accomplished through classical cytogenetic procedures (such as G-banding) combined with advanced molecular techniques such as FISH and genomic microarray analysis. The Coriell Institute Cytogenetics Laboratory provides not only detailed chromosomal analysis of all Coriell-banked human and animal cell lines available to worldwide genetic researchers, but also analyzes human and animal stem cell lines for academic research institutions and pharmaceutical clients engaged in cutting-edge stem cell research.
Laboratory Test Offerings
Molecular pathology is a crossover science that blends together practices of anatomic and clinical pathology while pulling ideas from biochemistry, molecular biology, proteomics and genetics with the emphasis on the sub-microscopic aspects of the sample being studied.
Chromosome disorders represent a large percentage of genetic disease. Approximately 30 percent of postnatal infant mortality is attributed to genetic disease in developed countries, while the incidence of chromosome abnormalities is relatively common in the general population. In a clinical setting, chromosome abnormalities account for a large proportion of cases involving spontaneous abortions; individuals with congenital malformations, mental retardation, infertility, women with gonadal dysgenesis, and couples with repeated spontaneous miscarriages. Cytogenetics is now being incorporated in the workup of patients already diagnosed with hematologic and oncologic disorders as well. Cytogenetic testing in this area is used not only for diagnosis, but also for classification of disease, decisions about treatment and to monitor disease progression and recovery.
Complex molecular testing can be expensive to implement and operate and is becoming more evident with labs forming to focus specifically on specialized testing, predictive testing and with existing labs incorporating more expansive test menus. While the physicians’ Current Procedural Terminology (CPT) has codes for molecular testing, pathologists need to ensure that the codes capture all the work done for a given molecular procedure when this testing is not being paid for by the patient (in many cases now a consumer-based model).
A Good Business Model
The multiple facets of molecular pathology testing can be incorporated into the business of the laboratory. Having the right LIS in a lab that offers these services to their providers enables that lab to capture the tests, results and codes necessary to thrive as this molecular pathology trend continues to grow. A flexible LIS designed to incorporate all clinical, pathology, molecular and billing information in a single database will separate a laboratory from its competition and ensure long-term profitability and a positive effect on its overall financial health. Having an LIS vendor that also provides a purpose-built, stand-alone molecular and cytogenetic LIS that focuses on the unique and specific needs and robust reporting and imaging requirements of these labs will enable a significant ROI for labs positioning for the long-term..