Expression of hypoxia-inducible factor-1α and vascular density in mammary adenomas and adenocarcinomas in bitches

Abstract

Background: The study aimed at examining hypoxia-inducible factor (HIF)1α expression in adenocarcinomas and adenomas in bitches in regard to tumour malignancy grade, proliferation, apoptosis and vascularisation. Therefore, paraffin sections of 15 adenomas and 64 adenocarcinomas sampled from 79 dogs aged 6 to 16 years were analysed.

Results: A significantly higher HIF-1α expression was noted in adenocarcinomas in comparison to adenomas (P < 0.0004). Moreover, HIF-1α expression in adenocarcinomas correlated positively with tumour malignancy grade (r = 0.59, P < 0.05), Ki-67 antigen expression (r = 0.43; P < 0.0005), TUNEL-positive cells (r = 0.62, P < 0001) and tumour vascularity measured by quantification of vessels characterized by the expression of von Willebrand Factor (r = 0.57, P < 0.05).

Conclusion: Results of this study indicate a similar biological role of HIF-1α in dogs and in humans, which may confirm suitability of the animal model in investigations on progression of tumours in humans.

Figure 1

Immunohistochemical expression of HIF-1α in adenoma (A) and adenocarcinoma (B). High expression intensity of Ki-67 antigen (C) and TUNEL in cancer cells (D). Von Willbrand Factor (vWF) expression in endothelial cells noted in adenoma (E) and adenocarcinoma (F). Magnification × 200 (A-D); ×40 (E-F).

Figure 2

Hypoxia-inducible factor-1α (HIF-1α) expression in adenomas and adenocarcinomas (A) and in relation to the grade of malignancy of the studied adenocarcinomas (B). ***P < 0.001; ****P < 0.0001, Mann–Whitney test.

Figure 3

Correlations between expressions of HIF-1α, Ki-67 antigen (A), TUNEL (B) and vWF MVD (C) in the analyzed adenocarcinomas.

Figure 4

Von Willbrand Factor mean vascular density (vWF MVD) in adenomas and adenocarcinomas (A) and in relation to the grade of malignancy of the studied adenocarcinomas (B). ***P < 0.001, Mann–Whitney test.