Investigation of serum Ki-67 as a biomarker in tumor-bearing dogs.

Because of the limited number of tumor markers in veterinary medicine, there is need for identifying new markers. Ki-67 has been investigated as a tissue marker of malignant alterations. We hypothesized that Ki-67 would also be measurable in serum and should therefore be elevated in cases of malignancy. The purpose of this prospective study was to measure Ki-67 in clinically healthy dogs, dogs with nonmalignant diseases, and dogs with malignant tumors. Samples from 8 healthy dogs, 13 dogs with nonmalignant diseases, and 20 dogs with malignant tumors were collected. Ki-67 was measured using the commercially available canine-specific ELISA. Results demonstrated undetectable Ki-67 serum concentrations in healthy dogs. Dogs with nonmalignant diseases displayed low Ki-67 serum concentrations. In contrast, dogs with malignancies showed significantly increased serum Ki-67 concentrations compared with the healthy (p<0.001) or nonmalignant diseased dogs (p<0.001). The degree of malignancy had a positive influence on serum Ki-67 levels. In contrast, no influence of tumor size on Ki-67 serum concentration was observed (p>0.05). Comparing healthy dogs and tumor bearing dogs a sensitivity of 0.75 and a specificity of 1.0 can be calculated using a Ki-67 cut-off value of 5.5pg/mL. When dogs with a low degree of malignancy were compared with dogs of moderate-to-severe degree malignant tumors a sensitivity of 1.0 and a specificity of 1.0 can be observed at a Ki-67 cut-off value of 19.25pg/mL. In conclusion, our results demonstrate an association of malignancies with elevated Ki-67 serum concentrations in dogs.

A large-scale association study to assess the impact of known variants of the human INHA gene on premature ovarian failure.

BACKGROUND: Three variants of the human INHA gene have been reported to be associated with premature ovarian failure (POF) in case-control studies involving a small number of patients and controls. Since inhibin has a fundamental role in the control of ovarian function, it is important to establish the relevance of the reported variants for disease risk. METHODS: Three independent POF cohorts, recruited in Northern and Central Italy and in Germany consisting of a total of 611 patients and 1084 matched controls, were genotyped for the three variants: -16C > T, -124A > G and 769G > A. RESULTS: No significant difference was detected between allelic frequencies of the INHA promoter variants between POF patients and controls. The rare allele in the coding variant appeared to be more frequent among the control populations. CONCLUSIONS: The association between the INHA promoter variants and POF could not be replicated, and our results suggest that this discrepancy is likely to be due to the small sample size of previous studies. The rare allele of the coding variant seems to exert a protective effect against loss of ovarian function, which should be confirmed in additional large and ethnically diverse cohorts.