The human proteome, due to the enormity of post-translational permutations that result in large numbers of isoforms, is much more complex than the genome and alterations in cancer can occur in ways that are not predictable by translational analysis alone. Proteomic analysis therefore represents a more direct way of investigating disease at the individual patient level. Furthermore, since most novel therapeutic targets are proteins, proteomic analysis potentially has a central role in patient care. At the same time, it is becoming clear that mapping entire networks rather than individual markers may be necessary for robust diagnostics as well as tailoring of therapy. Consequently, there is a need for high-throughput multiplexed proteomic techniques, with the capability of scanning multiple cases and analysing large numbers of endpoints. New types of protein arrays combined with advanced bioinformatics are currently being used to identify molecular signatures of individual tumours based on protein pathways and signalling cascades. It is envisaged that analysing the cellular 'circuitry' of ongoing molecular networks will become a powerful clinical tool in patient management.

The prognostic significance of c-erbB-2 expression was studied in paraffin wax embedded colorectal cancer tissue using a monoclonal antibody. One hundred and sixty-four patients with Dukes' B disease were studied. Membranous staining was not detected in any case. Cytoplasmic c-erbB-2 staining was seen in 55 cancers (33.5%). Cytoplasmic staining was unrelated to patient age (P = 0.31), sex (P = 0.69), tumour site (P = 0.69), size (P = 0.57), histological grade (P = 0.42) or ploidy status (P = 0.21) but was found more frequently in obstructing cancers (P = 0.03). Mean follow up of the patient population was 6.3 years. Five-year-survival estimated by the Kaplan-Meier life-table method was 47% for those with cytoplasmic c-erbB-2 staining and 77% for those without (log rank analysis; P < or = 0.0001). Stepwise regression analysis identified c-erbB-2 staining (relative risk, 2.51; P = 0.0005) and bowel obstruction (relative risk, 1.99; P = 0.015) as independent predictors of survival. It is suggested that cytoplasmic c-erbB-2 expression may provide a useful marker of tumour behaviour in Dukes' B colorectal cancer.

Formalin-fixed paraffin-embedded (FFPE) archival clinical specimens are invaluable in discovery of prognostic and therapeutic targets for diseases such as cancer.However, the suitability of FFPE-derived genetic material for array-based comparative genomic hybridisation (array-CGH) studies is under-explored. In this study, genetic profiles of matched FFPE and fresh-frozen specimens were examined to investigate DNA integrity differences between these sample types and determine the impact this may have on genetic profiles. Genomic DNA was extracted from three patient-matched FFPE and fresh-frozen clinical tissue samples. T47D breast cancer control cells were also grown in culture and processed to yield a fresh T47D sample, a fresh-frozen T47D sample and a FFPE T47D sample. DNA was extracted from all samples, array-CGH conducted and genetic profiles of matched samples were then compared. A loss of high-molecular weight DNA was observed in the FFPE clinical tissues and FFPE T47D samples, respectively. A dramatic increase in absolute numbers of genetic alterations was observed in all FFPE tissues relative to matched fresh-frozen counterparts. In future, alternative fixation and tissue processing procedures, and/or new DNA extraction and CGH profiling protocols, may be implemented, enabling identification of changes involved in disease progression through the use of stored clinical specimens.