Oncology

Clinical oncology is undergoing a dramatic transformation with elucidation of the fundamental molecular mechanisms of cancer, and the introduction of new forms of treatment that specifically target these processes. Although molecular targeted therapies offer the hope of more effective and less toxic treatment for cancer patients, their rational use in the clinic will require a sophisticated analysis of tumour tissue to determine if the target is being aberrantly expressed in an individual patient, and to allow therapy monitoring. Single cell measurements using flow cytometry or digital image analysis have the potential to play a major role in this process because they are quantitative, capable of measuring several molecular targets simultaneously, and address the problems of tumour heterogeneity.

Flow cytometry is being extensively used in the analysis of hematological malignancies. Surface immunophenotyping, an established diagnostic procedure in clinical laboratories, continues to develop with the introduction of newer surface markers, instrumentation and analysis platforms. Increasingly this is being complemented by newer methods that probe underlying molecular mechanisms that influence treatment sensitivity or biological aggression, or track the existence of minimal residual disease. Flow cytometry also has the potential to monitor residual disease in solid tumour patients through the detection of rare circulating tumour cells in the peripheral blood or bone marrow.

Digital microscopy lends itself more readily to the analysis of solid tumours than does flow cytometry, since it does not require disruption of tissue architecture to produce single cell suspensions. Historically this field has focussed on texture analysis, DNA content and cell cycle measurements, and more recently on cytogenetics. However, developments in probe technology, optical microscopy and computing, coupled with a deeper understanding of the basic cellular processes of cancer, will greatly extend the scope of image analysis applications in oncology over the next few years.
Examples of future applications include the assessment of tumour angiogenesis, aberrant regulation of signal transduction pathways, and treatment sensitivity markers. This approach will become increasingly powerful with the development of analytical methods that can address multicolour fluorescence measurements in the spatial domain, since it would then be possible to directly relate complex cellular processes to conventional histopathology. The image to the left shows a tiled field multicolour fluorescence image of a ME180 cervix cancer xenograft. The colours are micro blood vessels (CD31 - green); vascular perfusion using Hoechst-33342 (blue), and hypoxia using the nitroimidazole probe EF5 (red).
	David Hedley, March 2001