ABSTRACT
BACKGROUND: Angiogenesis is the highly ordered formation of new blood vessels from pre-existing vessels. It is seen throughout growth, in wound healing, menses, and is important in cancer, where pro- and antiangiogenic signals can be released by cancer cells, endothelial cells, stromal cells, blood, and the extracellular matrix. Aim of the study is to use standardized method for counting blood vessels to verify the significance and prognostic value of assessing marrow angiogenesis at diagnosis of de novo acute leukemia. SUBJECTS AND METHODS: The study included 70 newly diagnosed acute leukemia cases and a control group composed of 35 bone marrow biopsy sections obtained from breast cancer patients. Examination of CD34 immunohistochemically stained sections for the assessment of marrow angiogenesis by quantification of its microvessel density (MVD). RESULTS: MVD was significantly increased in acute leukemia patients in comparison to control group (P-value <0.001). Increased MVD was associated with unfavorable outcome. CONCLUSION: The study demonstrated an evidence of increased angiogenesis in acute leukemia detected by high bone marrow MVD which may play a significant role in leukemic process. Understanding its role may help in designing new therapeutic strategies for acute leukemia.
Subject(s)
Bone Marrow/pathology , Leukemia, Myeloid, Acute/diagnosis , Microvessels/pathology , Neovascularization, Pathologic/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Adolescent , Adult , Aged , Antineoplastic Agents/therapeutic use , Bone Marrow/blood supply , Bone Marrow/drug effects , Breast Neoplasms/blood supply , Breast Neoplasms/pathology , Child , Child, Preschool , Female , Humans , Immunohistochemistry , Induction Chemotherapy/methods , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Male , Microvessels/drug effects , Middle Aged , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/mortality , Neovascularization, Pathologic/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Prognosis , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND & PURPOSE: In planning diagnostic or follow-up investigational strategies, neuroblastoma (NB) metastatic deposits in bone and/or bone marrow (BM) should be detected as early as possible. Therefore, all investigational detection tools should be conducted simultaneously for precise staging. However, because of the financial conditions in our developing countries and in view of the cost/benefit relationship, the question is, can one detection tool only become satisfactory and replacing others? The purpose of our study is to compare simultaneous results of bone and metaiodobenzylguanidine (MIBG) scans versus BM biopsies with immunohistochemical (IHC) staining; in detecting bone and/or BM metastatic deposits in NB patients. MATERIAL AND METHODS: This study included 138 NB patients; 46 were de novo and 92 were under follow-up. They were subjected to bilateral BM biopsies, IHC staining (using NSE McAb) and Tc-99m methylene diphosphonate (Tc-99m MDP) bone scan (BS). Only 57/138 patients were, in addition, subjected to I-131 MIBG scan. RESULTS: Matched results between IHC-stained BM sections and bone scans (BSs) 107/138 (77.5%) were higher than the un-matched ones 31/138 (22.5%). There was a moderate agreement between the two methods in all studied cases (Kappa=0.538) and it was higher among de novo (Kappa=0.603) than follow-up group (Kappa=0.511). Among the 31 un-matched results, the most frequent (17/31) were due to the presence of minute amount of infiltrating NB cells that could be detected by IHC-stained BM sections and not by BSs. The less frequent (12/31) were due to the presence of metastatic deposits outside pelvic bones that could be detected by BSs and not by IHC-stained BM sections mainly in the follow-up cases (11/12) rather than de novo cases (1/12). The matched results between IHC-stained BM sections and MIBG scans 54/57 (94.7%) were higher than the un-matched ones 3/57 (5.3%). The agreement between the two methods was higher among de novo (Kappa=1.000) than follow-up group (Kappa=0.847). The agreement between IHC-stained BM sections and MIBG scans was substantial (Kappa=0.890) while that between IHC-stained BM sections and BSs was moderate (Kappa=0.538). CONCLUSIONS: We suggest a step-wise strategy to be applied, at least in developing countries, in approaching de novo and follow-up NB cases for detecting bone and/or BM metastatic deposits. This strategy might be beneficial if it is considered during application of NB guide-lines for diagnosis and follow-up.
