Intratumoural and Peritumoural Lymphangiogenesis in Canine Mammary Tumour Linked to Tumour Spread and Poor Survival

Canine mammary tumour (CMT) is an excellent, naturally occurring animal model for human breast cancer. Most research, so far, has focused on angiogenesis as a mode of tumour invasion and metastasis, but the role of lymphangiogenesis in mammary tumours is scarcely documented. The present study was conducted on 45 cases of CMT and the extent of lymphangiogenesis, demonstrated as intratumoural vessel density (IVD) and peritumoural vessel density (PVD) was determined by immunohistochemical staining with lymphatic markers, viz. podoplanin, LYVE-1, PROX 1 and VEGFR-3. The highest vessel density in intratumoural area was recorded with VEGFR-3 (35.94 ± 3.45), followed by podoplanin (31.95 ± 2.77), LYVE-1 (11.11 ± 2.20) and PROX 1 (7.62 ± 1.11). In peritumoural areas, the vessel density was highest with podoplanin (11.48 ± 1.32), followed by VEGFR-3 (7.69 ± 0.51), LYVE-1 (5.19 ± 0.96) and PROX 1 (3.48 ± 0.48). The lymphatics in intratumoural areas were small, thin and collapsed, whereas the peritumoural lymphatics were large and conspicuous. Overall survival was less in patients with high lymphatic density in peritumoural areas for podoplanin, and with high vessel density in intratumoural areas for VEGFR-3. The survival was also low in cases with lymphatic tumour emboli. It was concluded that both intratumoural and peritumoural lymphangiogenesis seemed to play significant role in tumour invasion and spread rather than peritumoural lymphatics. Moreover, the podoplanin and PROX 1 were found to be more specific markers of lymphangiogenesis.