Morphometric Approach to Angiogenesis In Acute Leukemia: An Attempt to Bring Objectivity

Shipra Verma; Deepti Mutreja; Boruah Dibyajyoti; Venkatesan S

doi:10.21276/apalm.3188

Shipra Verma Dept of Pathology, Command Hospital(SC), Pune, India
Deepti Mutreja Dept of Pathology, AFMC, Pune, India
Boruah Dibyajyoti Dept of Pathology, AFMC, Pune, India
Venkatesan S Dept of Pathology, R&R, Delhi, India

DOI: https://doi.org/10.21276/apalm.3188

Keywords: Leukemia, angiogenesis, microvessel density, morphometry

Abstract

Background:Angiogenesis is central to growth and development of all tissues, whether they are healthy or diseased. Angiogenesis has a key role in progression of tumor and in its metastasis and invasion. The role of angiogenesis in solid tumors is well established through various studies, but the same needs to be studied more extensively with respect to hematological malignancies. This could aid in prognostication and has therapeutic implications. The aim of the present study was to evaluate bone marrow microvessels in cases of acute leukemias by morphometry, for the purpose of providing objectivity, and study the angiogenic activity in these cases. Methods:In this study, all retrospective and prospective cases of acute leukemias diagnosed on bone marrow biopsies over a period of two years, from 2018 to 2020, were included. A total of 46 cases and 27 controls were studied. Hematoxylin and Eosin (H&E) and CD34 stained bone marrow biopsies were reviewed. For quantification of microvessel density (MVD), three “hotspots” (areas with maximum number of microvessels) on bone marrow biopsy were identified by scanning at x100 power. Then, at x400 magnification, the field was set to cover the maximum number of microvessels within the hotspot, and microvessels were counted in one field in each of the three hotspots. MVD was reported as the mean of the three hotspots expressed as the number of microvessels per mm2. The mean values of the measurements in the three fields were used for statistical analysis. Result: The cases of acute leukemia were found to have significantly higher MVD as compared to the control group. Present study also found significant correlation of MVD with marrow fibrosis and blast percentage in peripheral blood. However, the mean MVD did not show any significant correlation with the bone marrow cellularity. A significant reduction in MVD was found post therapy in the remission cases, while MVD was still high in case with relapse. Conclusion: There is a definite role of angiogenesis in pathophysiology of hematological malignancies. Assessment of bone marrow MVD by morphometry can help in lending objectivity to angiogenesis, which can aid in prognostication and therapeutics in cases of acute leukemias.

References

Jothilingam P, Basu D, Dutta TK. Angiogenesis and Proliferation Index in Patients with Acute Leukemia: A Prospective Study. Bone Marrow Res. 2014;2014:1–7.

Gullmann C, Dennis D, Mcmahon C, Jeffers M, Pule MA. Increased angiogenesis in bone marrow of children with acute lymphoblastic leukaemia has no prognostic significance. 2002;991–8.

Choi WWL, Lewis MM, Lawson D, Yin-Goen Q, Birdsong GG, Cotsonis GA, et al. Angiogenic and lymphangiogenic microvessel density in breast carcinoma: Correlation with clinicopathologic parameters and VEGF-family gene expression. Mod Pathol. 2005;18(1):143–52.

Şener E, Şipal S, Gündoğdu C. Comparison of microvessel density with prognostic factors in invasive ductal carcinomas of the breast. Turk Patoloji Derg. 2016;32(3):164–70.

Svagzdys S, Lesauskaite V, Pavalkis D, Nedzelskiene I, Pranys D, Tamelis A. Microvessel density as new prognostic marker after radiotherapy in rectal cancer. BMC Cancer. 2009;9:1–8.

Hasan J, Byers R, Jayson GC. Intra-tumoural microvessel density in human solid tumours. Br J Cancer. 2002 May 20;86(10):1566–77.

Kalmanti L, Dampaki K, Dimitriou H, Stiakaki E, Chaniotis V, Stathopoulos E. A morphometric approach for the evaluation of angiogenesis in acute lymphoblastic leukemia of childhood. Leuk Res. 2005;29(6):673–7.

Hussong JW, Shami PJ. Hussong JW , Rodgers GM , Shami PJ. Evidence of increased angiogenesis in patients with acute myeloid leukemia . Blood 95 (1): 309-313.

Mizia-Malarz A, Sobol-Milejska G. Assessment of angiogenesis in children with acute lymphoblastic leukemia based on serum vascular endothelial growth factor assay. Indian J Med Paediatr Oncol. 2017;38(3):321.

Schneider P, Dubus I, Gouel F, Legrand E, Vannier JP, Vasse M. What role for angiogenesis in childhood acute lymphoblastic leukaemia? Adv Hematol. 2011.

Trujillo A, McGee C, Cogle CR. Angiogenesis in Acute Myeloid Leukemia and Opportunities for Novel Therapies. J Oncol. 2012;2012:1–9.

Aref S, Salama O, Shamaa S, El-Refaie M, Mourkos H. Angiogenesis factor pattern differs in acute lymphoblastic leukemia and chronic lymphocytic leukemia. Hematology. 2007;12(4):319–24.

Perez-atayde AR, Sallan SE, Tedrow U, Connors S, Allred E, Folkman J. Short Communication Spectrum of Tumor Angiogenesis in the Bone. Am J Pathol. 1997;150(3):815–21.

Najafabadi MM, Shamsasenjan K, Akbarzadehalaleh P. Angiogenesis status in patients with acute myeloid leukemia: From diagnosis to post-hematopoietic stem cell transplantation. Int J Organ Transplant Med. 2017;8(2):57–67.

Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017;7(6):e577.

Rathee R. Acute Lymphoblastic Leukemia : Characterization and its Prognostic Values. 2013;2(December 2008):27–36.

De Kouchkovsky I, Abdul-Hay M. ‘Acute myeloid leukemia: A comprehensive review and 2016 update.’ Blood Cancer J. 2016;6(7).

Khawandanah M, Gehrs B, Li S, Holter Chakrabarty J, Cherry M. A Case of Acute Myeloid Leukemia with a Previously Unreported Translocation (14; 15) (q32; q13). Case Rep Genet. 2014;2014(16):1–4.

Haouas H. Angiogenesis and acute myeloid leukemia. Hematology. 2014;19(6):311–23.

Aguayo A, Estey E, Kantarjian H, Mansouri T, Gidel C, Keating M, et al. Cellular vascular endothelial growth factor is a predictor of outcome in patients with acute myeloid leukemia. Blood. 1999;94(11):3717–21.