Assessment of malignancy in canine cortisol-secreting adrenocortical tumors (ATs) remains challenging. No previous studies have linked molecular markers to survival times in dogs after adrenalectomy, making it difficult to give a reliable prognosis. The aim of this study was to identify molecular prognostic markers in a large cohort of canine ATs. This could not only enhance insight in individual prognosis, but could also provide potential future treatment targets.
Fifty-nine dogs with hypercortisolism due an AT that underwent adrenalectomy between 2002 and 2015 at the authors’ institution and of which follow-up information was available, were included in this study. Three classes of potential prognostic factors were reviewed: firstly clinical data, including body weight, age at time of surgery, gender, neuter status and tumor size; secondly immunohistochemical Ki67 labeling index, and thirdly mRNA expression of factors associated with proliferation of ATs, including SF-1, PTTG1, PBX1, VAV2, RRM2, TOP2A, Ki67, CCND1, MC2R and BCL2. Univariate analysis was performed with the Cox proportional hazards model for continuous variables and the Log Rank test for bivariate variables. Multivariate analysis was performed using multiple linear regression with forward selection.
Median survival time was 63.6 ± 9.4 months. In the univariate analysis, significant prognostic factors were tumor volume in cm3 (P=0.015, hazard ratio (HR)=1.004), maximal diameter of tumor in cm (P=0.047, HR=1.284), Ki67 labeling index (P6) as independent predictors of poor survival.
In conclusion, most important predictors of poor survival are Ki67 labeling index and SF-1 expression. These results show the importance of including Ki67 staining in histopathological assessment of canine ATs. Moreover, since pharmacological manipulation of SF-1 is possible, the considerable impact of SF-1 expression on prognosis indicates great potential of SF-1 as a treatment target in canine ATs in the near future.
Faculty of Veterinary Medicine, Utrecht University
I finished my Master Companion Animal Medicine at the end of 2014, and started working as a PhD candidate at the beginning of 2015. My research is focused on canine hypercortisolism, with a special interest in cortisol-producing adrenocortical tumors. My first publication was on the functional zonation of the canine adrenal cortex, where we found that, contrary to what can be read in most text books, canine steroidogenesis is not completely identical to that of humans. Additionally, I am focused on testing possible future treatment options for canine hypercortisolism in canine primary adrenocortical cell culture, which is a valuable method to test compounds preclinically and thereby reduce the number of laboratory animals that are required. Lastly, I am also interested in how we can predict the prognosis of dogs with cortisol-secreting adrenocortical tumors after they underwent adrenalectomy. For a part of this study, I was incredibly happy to receive the first price at the European Society of Veterinary Endocrinology stream at the ECVIM-CA congress 2017, which is why I am now able to present this to you at the ACVIM Forum 2018. I am looking very much forward to it.
Thursday, June 14
1:30 PM – 1:45 PM
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