Heterotopic bone formation in tumor stromal tissue. Immunohistochemical considerations.

Abstract

Ectopic and heterotopic bone formation rarely occur in stromal tissues of various epithelial tumors. In the present study, ectopic bone forming tumors; calcifying epithelioma Malherbe (6), renal cell carcinoma (1), thyroid adenocarcinoma (1) and ovary carcinoma (1) were examined. The process of ectopic bone formation could be classified into 1) bone formation related to epithelial tissue as found in calcifying epithelioma of Malherbe, 2) bone formation from perivascular smooth muscle, and 3) that due to metaplasia occurring in stromal connective tissue of epithelial tumors. Immunohistochemical detection of proteoglycans (PG) was made in bone-forming matrix areas, and these areas were positive for chondrotin 4 and 6 sulfate, and dermatan and heparan sulfate PGs. Immunohistochemically, fibronectin, collagen III and bone sialoprotein as matrix proteins, and carbonic anhydrase as calcification marker were tested and they appeared in these pre-calcifying tissues.

Immunohistochemistry with keratin, vimentin, desmin, and α‐smooth muscle actin monoclonal antibodies in canine mammary gland: Benign mammary tumours and duct ectasias

“…In canine benign mixed mammary tumours, transition of myoepithelial cells to cartilage has been documented by electron microscopical and histochemical studies examining chondroitin sulphuric acid and alkaline phosphatase (30,47,58). Transformation of modified myoepithelial cells has also been reported in humans (2,17,28,33) and the origin of pleomorphic adenoma of the breast from a single cell type capable of bidirectional differentiation has been suggested (14). However, our findings strongly suggest that cartilage and/or bone formation in canine mammary tumours results from stromal metaplasia, which is in line with histochemical studies concerning anionic heteroglycans (45).…”

“…However, our findings strongly suggest that cartilage and/or bone formation in canine mammary tumours results from stromal metaplasia, which is in line with histochemical studies concerning anionic heteroglycans (45). This stromal metaplasia is a wellknown phenomenon in the stroma of epithelial tumours at different sites (33). In the canine fibroadenomas of the benign mixed type, a small number of cells positive for the basal cell keratins was found within the chondroid or osteoid matrix.…”

Expression of Bone Morphogenetic Protein-6 and Bone Morphogenetic Protein Receptors in Myoepithelial Cells of Canine Mammary Gland Tumors

“…10,17,18 BMPs are multifunctional proteins originally isolated from bone and are identified by their ability to induce ectopic cartilage and bone formation. 1,16 BMPs regulate various aspects of organogenesis during development 13,23 and osteogenesis. 24 These proteins also have been detected in various mesenchymal and epithelial tumors, and they participate in ectopic ossification or epithelial-mesenchymal interaction.…”

“…24 These proteins also have been detected in various mesenchymal and epithelial tumors, and they participate in ectopic ossification or epithelial-mesenchymal interaction. 9,10,[16][17][18]29,34,35 It has been found that type IV collagen is important for the actions of BMPs because some types of BMPs, such as BMP-2 and BMP-7, can intimately bind to type IV collagen. 8,25 BMP-2 coexisting with type IV collagen induces psammoma bodies in human ovarian cancer.…”

Glycosaminoglycan Distribution in Chondro-Osteogenesis Induced by Bone Morphogenetic Protein in Mouse Muscle Tissue with the Use of Monoclonal Antibodies.

“…Thus, GAGs were found to occur specifically in the 1st stage of the BMP-implanted area. Fibrous or metaplastic ossification was reported to occur in connective tissue cells as seen in tumor stromal ossification (15,16,18,21) or experimental bone induction by urinary bladder transplantation (7,11). It is significant that BMP does not directly induce the replacement of bone tissues, but BMP directly induces the proliferation of neighboring undifferentiated mesenchyme cells, and these cells then induce chondroidal metaplasia.…”