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 (p<0.001, HR=1.220) and mRNA expressions of SF-1 (p=0.021, HR=60.244), PTTG1 (p=0.024, HR=12.321), PBX1 (p=0.005, HR=8.714), and TOP2A (p=0.035, HR=7.191). Forward stepwise multivariate analysis identified Ki67 labeling index (p=0.024, HR=1.574) and SF-1 mRNA expression (p=0.044, HR= 1.936*10⁶) 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.

Disclosures

No disclosures to report.