Expression of bone morphogenetic proteins in colon carcinoma with heterotopic ossification

Abstract

Here we report the case of a 50-year-old woman with adenocarcinoma of the colon, showing heterotopic ossification. The patient was referred to our hospital for investigation of anemia secondary to occult gastrointestinal blood loss. By colonoscopy, an irregular polypoid mass was found in the ascending colon. A biopsy of the lesion revealed moderately to poorly differentiated adenocarcinoma with heterotopic ossification. A right hemicolectomy was done and revealed areas of heterotopic bone within the tumor, but no ossification was evident in the metastatic lesions within the mesenteric lymph nodes. The formation of heterotopic bone in gastrointestinal tumors is rare and its exact mechanism is unknown. Immunohistochemical localization of bone morphogenetic proteins (BMP), known to be primary inducers of new bone formation, was determined. BMP-5 and -6 were prominent in the cytoplasm of tumor cells, and they stained weakly in osteoblast-like cells adjacent to newly formed bone. Cytoplasmic staining for BMP-2 and -4 was weak in tumor cells, osteoblast-like cells, and stromal fibroblast cells. BMP may play an important role in heterotopic ossification in colon adenocarcinoma.

Ossified choroid plexus papilloma of the fourth ventricle: elucidation of the mechanism of osteogenesis in benign brain tumors

“…4,18,25 Differentiation of these mesenchymal cells into osteoblasts causes production of BMPs, factors necessary for bone formation. In a previous analysis reported by Imai et al, 9 BMP-5 and BMP-6 were present in all tumor cells from an ossified colon cancer, with BMP-2 and BMP-4 present in only the cells surrounding the sites of ossification. It is thought that BMP-5 and BMP-6 expression induces differentiation of surrounding mesenchymal cells into preosteoblasts that express BMP-2 and BMP-4.…”

“…It is thought that BMP-5 and BMP-6 expression induces differentiation of surrounding mesenchymal cells into preosteoblasts that express BMP-2 and BMP-4. 9 In ossified rectal and lung cancers, BMP-2 has been found to be expressed in many tumor cells. 16,31 Additional factors are needed for bone maturation, namely Runx2 and osterix; VEGF also assists in the differentiation and migration of hematopoietic cells into the spaces between trabeculae to form marrow.…”

“…21 Imai et al 9 have proposed heterotopic ossification occurring through metaplasia of the tumor stromal tissue. Bone morphogenetic protein is known to produce ectopic bone formation when introduced into normal muscle tissue; 9 de-differentiated tumor cells expressing BMP could lead to the ossification seen in these tumors.…”

Overexpression of bone morphogenetic protein 2 through aberrant canonical Wnt/β-catenin signaling pathway plays an important role in heterotopic ossification of adrenal myelolipoma

“…Previous studies have shown that bone morphogenetic protein 2 (BMP2), known to be a primary inducer of bone formation, plays an important role in heterotopic ossification in several types of cancer. [1][2][3] Interestingly, a more recent study found that coordination of BMP2 and Wnt/β-catenin signaling may be involved in the process of osteoplastic differentiation and subsequent bone formation, 4 while β-catenin has also been reported to induce BMP2 expression in gastrointestinal cancer cells. 5 We report a case of adrenal ML showing heterotopic bone formation with overexpression of BMP2 and β-catenin, indicating the possible involvement of BMP2 and the Wnt/β-catenin signaling pathway in heterotopic ossification.…”

Association of BMP6 Methylation and Expression with Clinicopathological Features in Colorectal Cancer

“…In addition, BMP6 has been report that it may play an important role in heterotopic ossification in colon adenocarcinoma. It is prominent in the cytoplasm of tumor cells, and it stains weakly in osteoblast-like cells adjacent to newly formed bone [11]. On the other hand, several reports suggested that BMP6 promoter methylation status is correlated with cancer.…”