Pathology supported genetic testing

Pathology supported genetic testing

Numerous new technologies have been introduced into the routine pathology laboratory over recent years. The growing number of new specialties in medicine and pathology furthermore re led to the introduction of modern evidence based medicine and major advances in our understanding of disease processes and their diagnosis.

The diagnostic process begins with clinical observations and the need for objective and accurate pathological assessments to arrive at a specific diagnosis. Pathology results, similar to genetic test results, are interpreted within a clinical context as an accurate diagnosis depends on careful clinic-pathological correlation. Advanced technologies are increasingly used to stay abreast of expanding clinical requirements such as sub classification of cardiovascular diseases (e.g dyslipidaemia, venous thrombosis, cardiomyopathy) and prognostication of patients with breast carcinoma to guide the direction of therapeutic intervention. Through clinic-pathological correlation, all laboratory results including those obtained through molecular genetic applications, are finally interpreted and integrated with the patient's clinical findings and data from other special investigations. Identification of genetic subgroups at risk of drug side effects or with different treatment or dietary requirements provides a scientific basis for targeted intervention as opposed to a one-size-fits-all approach.

It is important to develop innovative approaches to risk management of complex multifactorial diseases, which could be applied in a clinical context where the genetic test results are fully integrated with relevant clinical information and other diagnostic pathology data. Provision of clinically-useful genetic information requires careful review of the literature to prevent the use of genetic alterations of unknown functional significance in genetic tests.

Where genetic tests, similar to some non-genetic pathology tests, have not been adequately validated the scarcity of sound scientific evidence rightfully challenges the ethical and scientific justification of routine application of these tests in clinical practice. However, the growing clinical demand for such tests pertaining for example to pharmacogenetics and nutrigenetics - to identify genetic determinants of differential responses to medical treatment or dietary intervention - drives the need to offer such tests in an appropriate clinical context and as part of an integrated pathology-based platform. Such an approach is often a logical addition to and expansion of well-established clinical practice to sub-classify complex diseases into treatable entities. A good example is cardiovascular disease referred to in more detail below, where correlation between the presence of well-established genetic and lifestyle risk factors and relevant biochemical profiles could be used to determine gene expression and monitor response to the intervention strategy applied.

Pathology supported genetic testing involves five steps:
  • Document family history and evaluate the patient?s current health status
  • Choose appropriate genetic test(s) based on the medical history and lifestyle risk factors
  • Combine information obtained in 1 and 2 into an informative test report, providing risk implications and health guidelines based on gene expression, if any
  • Apply test information to rectify gene-environment mismatches that may be reflected as biochemical abnormalities or clinical symptoms
  • Monitor response to treatment as part of compliance management

Figure 1: Risk management genetic testing includes evaluation of the current health status of the individual, documentation of the family history and pathology supported gene-based intervention, based on the overall risk profile.

The future

The rapidly expanding global interest in molecular genetic testing for the early detection of disease and the subsequent opportunity for preventative or therapeutic interventions to influence the outcome of a disease, confirms the importance of this new field in healthcare. The need for pathology tests including molecular genetic tests is primarily determined by clinical need as defined by patients expectations and clinicians demand for relevant information to guide the clinical management of patients, including the prevention of disease through appropriate interventions. Other relevant drivers for laboratory tests include current developments in health science, health economy including medical aid policies, and evidence-based guidelines pertaining to the diagnosis and clinical management of patients.

Numerous and major advances characterized the evolution of modern medicine during the past centuries and brought about many changes to the practice of clinical and diagnostic health sciences. The rapidly expanding integration and overlapping of traditionally distinctly separate fields of medicine introduced a new era of interdisciplinary - and team-approaches to clinical practice and patient care. In this regard, clinical human genetics including molecular genetics is indeed no exception. Matching disease diagnosis and therapeutic design with the clinical picture, pathology, environmental risk factors and genetic profile of the patient is a rapidly evolving era that will become increasingly important.


  1. S.J. van Rensburg, M.J. Kotze and R. van Toorn (2012) The conundrum of iron in multiple sclerosis – time for an individualized approach, Metab Brain Dis (2012) 27:239–253
  2. M.J. Kotze and S.J. van Rensburg, (2012) Pathology supported genetic testing and treatment of cardiovascular disease in middle age for prevention of Alzheimer’s disease, Metab Brain Dis (2012) 27:255–266

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