Lymphangiogenesis in Hodgkin Lymphoma and in Indirectly Related Conditions – A Review

Author(s): Daniel Benharroch, Isebrand Prinsloo, Jacob Gopas, Benzion Samueli

The significance of lymphangiogenesis in malignant tumors and specifically in classic Hodgkin lymphoma has not been properly evaluated, in contrast with that of angiogenesis in these neoplasms. In the study reviewed herein, the relevance of lymphatic vessel proliferation was explored in 19 cases of classic Hodgkin lymphoma stained with the D2-40 (anti-podoplanin) antibody. In each case, three lymphatic vessel hot spots were analyzed twice. Of the 57 hot spots thus investigated, 15 were chosen at random for image acquisition and analysis and microvessel counting. The mean perimeter, major axis length, surface area and complexity factor for each hot spot were established by morphometry, and associations with clinical and laboratory traits of classic Hodgkin lymphoma were identified. No relationships were found with the clinical features or immunostaining for typical markers of this lymphoma. However, significant inverse relations were found with BAX, pRb and IκB-α expression in tumor cells, genes believed to play roles in apoptosis in this lymphoma. The mean lymphatic major axis length was inversely correlated with the complexity factor. Clinicopathological associations were further obtained for the expression of BAX, pRb, and IκB-α in a large cohort of classic Hodgkin lymphoma patients that was previously published. Since the issue was poorly explored at this point, we have reviewed the significance of lymphangiogenesis in indirectly associated conditions.