Prognostic Value of Immunohistochemical Angiogenic and Invasion Markers in Hodgkin Lymphoma.

Microenvironment has and important role in sustaining the malignant cells by providing survival signals and promoting angiogenesis and invasion. Vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), metalloproteinase-2 (MM2) and laminin are involved in angiogenesis, growth and metastatic invasion potential of malignancies. Numerous studies have demonstrated up-regulation of this protein at both mRNA and protein level in various tumours and a correlation with advanced stage and prognosis has been demonstrated in several solid tumors and hematologic malignancies such as multiple myeloma or non-Hodgkin lymphomas. There is evidence that also the neoplastic Hodgkin-Reed-Stenberg cells express VEGF and that VEGF expression both in macrophages and the extracellular matrix might facilitate tumour progression. To analyze the role of these markers in the prognosis we retrospectively examined their immunohistochemical expression using a tissue array in a series of 62 cases of Hodgkin’s disease uniformly treated with the standard ABVD regimen (3–6 cycles, in function of clinical prognostic factors). Median age was 30 years (14–71). Prognostic factors were as follows: 35% Ann Arbor stage III–IV, 23% adjusted-international prognostic index >1 and 11% Hasenclever > 3. Median follow-up was 90 months. Relapses were significantly higher in patients with strong VEGF staining (50% vs 19%; p=0.04) with a significant worst progression-free survival (60% vs 84%; p = 0.01). COX-2, MM2 and laminin showed a non-significant trend towards a lower relapse rate and PFS. Conclusion: The presence of VEGF strong staining in Hodgkin-Reed-Stenberg cells or reactive macrophages and the extracellular matrix might facilitate tumour progression as it was related to a shorter PFS. The trend towards a worst prognosis in higher COX-2, MM2 and laminin staining warrants further investigation of their role in the prognosis of patients with Hodgkin lymphoma.