Abstract
Angiogenesis is essential for tumor growth and metastasis, nevertheless, in NB, results between different studies on angiogenesis have yielded contradictory results. An image analysis tool was developed to characterize the density, size and shape of total blood vessels and vascular segments in 458 primary neuroblastic tumors contained in tissue microarrays. The results were correlated with clinical and biological features of known prognostic value and with risk of progression to establish histological vascular patterns associated with different degrees of malignancy. Total blood vessels were larger, more abundant and more irregularly-shaped in tumors of patients with associated poor prognostic factors than in the favorable cohort. Tumor capillaries were less abundant and sinusoids more abundant in the patient cohort with unfavorable prognostic factors. Additionally, size of post-capillaries & metarterioles as well as higher sinusoid density can be included as predictive factors for survival. These patterns may therefore help to provide more accurate pre-treatment risk stratification, and could provide candidate targets for novel therapies.
Highlights
Neuroblastic tumors (NB) cause 15% of childhood deaths by cancer [1]
In order to determine histological patterns associated with different degrees of malignancy, we developed a novel and accurate image analysis algorithm, capable of quantifying and characterizing blood vessels, and performed statistical analyses to correlate the resulting variables with the International NB Risk Group (INRG) prognostic features and the risk of relapse or death
Vascular invasion was observed in NB (Figure 1D, 1E)
Summary
Neuroblastic tumors (NB) cause 15% of childhood deaths by cancer [1]. Despite the definition by the International NB Risk Group (INRG) of seven clinical and biological parameters that interplay to define a very low to high risk of progression [2], greater efforts are needed to enhance survival, especially in the high-risk group. In NB, results between different studies on angiogenesis are conflicting, some indicate a prognostic value and others reject such conclusions [3,4,5,6,7,8] This discrepancy may be due to the different methods or materials utilized. The properties and composition of the vascular system may be associated with histological subtypes of NB and could be morphologically and topologically characterized and linked to patient prognosis This may provide more accurate pretreatment risk stratification or candidate elements for novel therapies. In order to determine histological patterns associated with different degrees of malignancy, we developed a novel and accurate image analysis algorithm, capable of quantifying and characterizing blood vessels, and performed statistical analyses to correlate the resulting variables with the INRG prognostic features and the risk of relapse or death
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