The role of C-reactive protein as a biomarker in dogs with lymphosarcoma

Fontaine, Samantha Joanna (2013) The role of C-reactive protein as a biomarker in dogs with lymphosarcoma. MSc(R) thesis, University of Glasgow.

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C-reactive protein (CRP) is a highly sensitive but non-specific acute phase
protein that is produced in the liver in response to injury, inflammation and
disease. CRP has been by shown by several authors to be elevated in dogs with
lymphoma (LSA) compared to healthy control dogs, however the findings of their
small studies have suggested that CRP is too non-specific to be used in a clinical
setting to monitor dogs with LSA that are receiving treatment with
chemotherapy. Studies in the human literature have shown that CRP
concentration is significantly affected by extent of disease and by the presence
of clinical signs in patients with both non-Hodgkin’s and Hodgkin’s lymphoma,
and it has been suggested that an elevated concentration of CRP at time of
diagnosis carries a poorer prognosis. No veterinary studies to date have been
large enough to investigate the effect of patient clinical parameters on CRP
concentration, or to determine whether CRP concentration carries any
prognostic significance.
The aim of this study was to determine whether serum CRP was a clinically
relevant biomarker in dogs with LSA using a large population. Specific aims
included confirming if differences existed between the CRP concentration of
healthy dogs and dogs with LSA, and determining if any patient variables had a
relationship with CRP concentration. The effect on CRP concentration in dogs
receiving chemotherapy treatment was investigated, with an aim to determine
whether CRP could be used for categorisation of remission status. Finally, the
role of CRP concentration as a prognostic indicator was investigated with respect
to disease relapse and survival.
This study included 59 control dogs and 73 dogs with LSA. Spare serum was
prospectively harvested and stored at -70°C prior to batch analysis on an
immunoturbidimetric assay (Pentra 400, Horiba ABX). Serial samples were
obtained at time of diagnosis, throughout treatment with chemotherapy, at
routine re-check appointments and at time of recrudescence of disease. Dogs
with LSA were fully staged at time of diagnosis to determine the extent of
disease and all dogs were assigned a WHO stage and substage. Of the dogs that
received treatment with chemotherapy, a remission status (i.e. complete/partial remission, stable disease or progressive disease) was assigned
at each visit based on the subjective response to treatment from the palpation
of peripheral lymph nodes. Patient clinical data was retrospectively obtained
from both paper and electronic records. CRP was investigated as both a
continuous and categorical variable, and categorisation was based on the degree
of elevation of concentration. Significance was set at a p-value of ≤0.05. CRP
concentration was deemed normal if ≤10 mg/L.

Results suggest that serum CRP concentration is significantly higher at time of
diagnosis in dogs with LSA compared to the control dogs, however not all dogs
with LSA exhibit an elevated CRP concentration. CRP concentration returns to
within normal limits for the majority of dogs following 4 weeks of treatment
with chemotherapy. Of the patient variables investigated, WHO stage and
substage, and pre-treatment albumin concentration were shown to be significant
following univariate analysis. Significant differences between the median CRP
concentration of the different remission statuses exists, however the overlap of
ranges of CRP concentration in each group suggests that it could not be used to
categorise remission status. The median CRP concentration at time of diagnosis
is significantly higher than at time of relapse of disease; however CRP
concentration does become elevated in most dogs at time of relapse. CRP
concentration was not shown to be significantly elevated in the weeks leading up
to relapse, indicating that this biomarker is not useful for predicting early
relapse prior to recrudescence of disease becoming clinically apparent. Finally,
results of the survival analysis revealed that pre-treatment CRP concentration is
not a significant variable, however immunophenotype and WHO substage are.
This is the largest study to date investigating CRP concentration in dogs with LSA
and is the first study to suggest a relationship between CRP concentration at
time of diagnosis and pre-treatment albumin, WHO stage and substage. Findings
from this study have confirmed those of previous authors; for example CRP
concentration becomes elevated in dogs with LSA both at time of diagnosis and
at time of relapse of disease, and that immunophenotype and WHO substage
carry prognostic significance. Although CRP concentration did not show any
prognostic significance, there was a trend for those dogs with a moderate and
marked elevation in CRP concentration (>30 mg/L) to have a reduced overall
survival time.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Subjects: S Agriculture > SF Animal culture > SF600 Veterinary Medicine
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Supervisor's Name: Morris, Dr. Joanna
Date of Award: 2013
Depositing User: Miss Samantha Joanna Fontaine
Unique ID: glathesis:2013-4078
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 13 Mar 2013 11:47
Last Modified: 08 Mar 2016 10:53

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