One of our founding goals was to be involved in clinical research and we are very keen to use our caseload for clinical research purposes. We are concentrating on prognostically-relevant, clinically-driven studies that could have a direct bearing on diagnosis, prognostication or treatment of veterinary patients. These studies have led to a number of recent publications in the veterinary literature, and we continue to pursue our research both independently and in collaboration with other academic institutes.
For instance, in a truly international study initiated at Bridge Pathology, and co-ordinated at the Univeristy of Guelph, cases of primary splenic lymphoma were accrued from institutions from around the world, to test the hypothesis that in some dogs, splenic lymphoma might be cured by surgery alone. In the study, that was recently published in Veterinary Surgery, we found that approximately 60% of primary splenic lymphomas were cured by surgery alone and that post-surgery chemotherapy did not improve clinical outcome. The results of this study suggest, that lymphoma that is confined to the spleen carries a potentially good prognosis in a significant percentage of dogs.
We expect that with increasing use of the recent WHO lymphoma classification scheme that we were involved in validating, that further lymphoma subtypes will be identified that have markedly different prognoses. For instance, the old dogma of ‘B-cell lymphomas are good, T-cell lymphomas are bad’ is looking increasingly incorrect. For instance, we frequently see cases of canine T-zone lymphoma, which has been shown to have a relatively favourable prognosis in dogs compared to many other lymphoma types. In some of the cases we have followed, such dogs have been treated by surgery alone without chemotherapy, and are still alive more than three years later.
We have been extensively involved in the outbreaks of acute renal failure in dogs, recently termed ‘Idiopathic Cutaneous and Renal Glomerular Vasculopathy’. Work by our colleague Ian Hawkins, who has just recently returned to work in the United States, confirms that this disease is very similar to ‘Alabama Rot’ and although the precise cause is still not known, is most likely to be the result of exposure to one or more bacterial toxins.
Over the past few years, we have been part of an international team of pathologists developing a new mast cell tumour grading scheme. You may have noticed that we have introduced this scheme as a standard part of our mast cell tumour reporting. We expect over the next few years that this new ‘Kiupel’ two-tier (high grade vs. low grade) scheme will be refined further, and that ultimately it may supercede the older, ‘Patnaik’ three-tier (high, intermediate and low grade) grading scheme. We still recommend the use of Ki67 immunohistochemistry to help predict prognosis for cutaneous mast cell tumours, especially those diagnosed as intermediate or low grade tumours. This assay does appear to identify a population of mast cell tumours that are histologically well differentiated, but that based on the Ki67 assay appear to have potential to behave in a much more aggressive manner than otherwise would be expected. Indeed, a recent study published in the Journal of Small Animal Practice, confirms that low Ki67 values accurately predicts survival, and that it has prognostic value independent of mitotic index alone. This study was published independently of Bridge Pathology, using Ki67 index values that we generated from mast cell tumour samples sent to us as diagnostic cases. This study further helps to confirm the utility of performing this prognostic assay in ‘real world’ situations.
Additionally, a new class of anti-cancer drugs – receptor tyrosine kinase antagonists – have become available for treatment of mast cell tumours. We have introduced a new immunohistochemical assay, that we can perform on routine biopsy specimens, that indicates whether kit (CD117) is expressed by these tumours. This protein is a major target for these drugs and demonstration of expression of this molecule in a tumour provides a rationale for their use in an individual animal. Indeed, we are currently investigating whether other tumour types express this protein and other similar receptor tyrosine kinases (PDGFRA, EGFR, etc), and therefore whether these drugs may be applicable for use in other tumour types. This type of individually tailored therapy is likely to become increasingly relevant as new classes of anti-cancer drugs become available for veterinary patients.
Similarly, we have recently added a new single immunohistochemistry test for those tumours where you may be considering using COX-2 antagonists. This assay is used to assess the extent of expression of COX-2 staining in tumour samples. There have been a lot of studies published in the veterinary literature examining the extent of expression of COX-2 in a range of cancers and inflammatory diseases. Unfortunately, it is very difficult to compare the results from these studies as each research group uses a different staining protocol, resulting in often conflicting results. To help resolve this issue, we have been involved in an international collaboration in order to agree on a standard for COX-2 immunohistochemical staining. Our laboratory has been instrumental in developing this staining protocol and this is the protocol that is now in use here and which we expect to be used in all future studies. We hope that this type of consensus- building study, will act as a model by which other immunohistochemical staining protocols can be developed in the future, and hence increase the chances of research fndings being directly translated into enhanced clinical practice. Our findings have been accepted for publication in the Journal of Comparative Pathology.
In 2015, we made a large investment in a state-of-the-art digital slide scanner. This enables us to capture digital scanned images of stained sections in incredible detail. We currently scan slides for three of our pathologists, allowing them to work off-site. In addition, the incredible images that we obtain from these scans, provides teaching materials which we currently share with students at the new veterinary school at the University of Surrey.