الفهرس | Only 14 pages are availabe for public view |
Abstract Bone marrow fibrosis, usually shown by silver (reticulin fibrosis) or trichrome (collagen fibrosis) stains, can accompany a wide variety of benign conditions and malignant disorders. The pathophysiology of bone marrow fibrosis in these disorders is just beginning to be elucidated. Most diseases with increased B.M fibrosis are associated with abnormalities of the number and/or function of megakaryocytes. A growing body of evidence suggests that TGF-β is a potent stimulator of fibroblast collagen synthesis, but it is likely that other cell types, cytokines and growth factors are also involved. CTGF is downstream mediator of TGF-β thereby playing a key role in biologic processes like wound healing or in pathological situations like fibrosis by promoting fibroblast proliferation, inducing ECM remodeling and initiating myofibroblast differentiation that deposits collagen, ultimately resulting in organ scarring and dysfunction. Assessment of CTGF expression in various tissues was done in many studies by variable laboratory techniques; among these techniques is immunohistochemistry. The aim of this study was to elucidate whether CTGF expression is increased in cases of bone marrow fibrosis and demonstrate whether CTGF expression differs with the type of underlying bone marrow disease. The present study included 50 B.M biopsy samples from archived coded cases at clinical pathology department, faculty of medicine, Cairo University. Selected cases were subjected to histochemical stains for fibrosis including silver impregnation for reticulin and trichrome staining for collagen. In addition to immunohistochemical staining for CTGF, Collagen types I and III. Cases included were classified into two groups according to trichrome staining: Fibrotic group included 13 cases with positive trichrome stain and nonfibrotic group included 37 cases with negative trichrome stain. On analysis of the collected data, it was found that: As regard reticulin staining, grade 3 and grade 4 were the most evident grades in the fibrotic group, while grade 0 was the most common grade represented in the non-fibrotic group. Regarding the results of reticulin staining in MPNs and metastatic groups, grades 3 and 4 were the most common represented grades while, grade 0 was the most common represented grade in LPDs, AL and reactive B.M changes groups. Immunohistochemical staining of collagen I and III showed that grade 4 was the most evident grade represented in the fibrotic group while grade 0 was the most common grade represented in the non-fibrotic group. Regarding collagen I and III staining in MPNs and metastatic group, grade 4 was the most common represented grade while in LPDs, AL and reactive marrow groups, grades 0 and 1were the most common represented grades. Positive staining of CTGF was detected in megakaryocytes, granulocytes, endothelial cells lining vascular channels, fibroblasts, myeloma cells and metastatic tumour cells. CTGF expression in stromal cells and tumour cells was more common in fibrotic group than in non-fibrotic group, which proves CTGF as an important factor in pathogenesis of bone marrow fibrosis. In conclusion, CTGF was highly expressed in stromal cells as well as tumour cells in fibrotic marrows than non-fibrotic marrows coinciding with collagen I and III. CTGF was also highly expressed in metastatic bone marrow proving its role in promoting bone marrow fibrosis as well as tumour invasion and metastasis in some tumours so it may be a potential novel therapeutic target for both conditions. |