title: Comparison of histological changes and changes in nm23 and c-MET expression between primary and metastatic sites in osteosarcoma: a clinicopathologic and immunohistochemical study.
abstract: Changes in morphological features between the primary and metastatic sites in osteosarcoma and the role of nm23 protein and c-MET oncogene product have remained controversial. In addition to histological studies, we evaluated the expression of nm23, c-MET, p53, and MDM2 immunohistochemically using 25 osteosarcomas in which both primary and concordant metastatic specimens were available. Moreover, we assessed proliferative activity using the monoclonal antibody MIB-1. Among these 25 cases, 4 tumors that were osteoblastic type (16%) in the primary site had changed morphologically to MFH-like type in the metastatic site, whereas 2 MFH-like type and 1 small cell-type tumors had changed to osteoblastic type. MIB-1 LI was significantly higher in the metastatic site than in the primary site (primary, 20.02; metastatic, 26.72; P = .0209). Seventeen cases (68%) showed increased nm23 expression in the metastatic site, whereas 2 cases showed reduced expression. nm23 expression was significantly increased in the metastatic site, compared with the primary site (P = .0009). Seven cases (28%) showing negative reaction for c-MET in the primary site showed immunuoreactivity for c-MET in the metastatic site. Although there was no statistical significance, c-MET expression seemed to be more frequent in the metastatic site, compared with the primary site. Among the overall tumors, c-MET-positive tumors showed significantly higher MIB-1 LI, compared with c-MET-negative tumors (negative, 20.99; positive, 27.65; P = .0292). No significant change was observed regarding p53 and MDM2 between the primary and metastatic site. Our results suggest that rather than being a metastasis-suppressor gene, nm23 is in fact correlated with metastatic progression in osteosarcoma. Positive correlation between c-MET expression and proliferative activity also suggests that c-MET expression may play an important role in tumor progression in osteosarcomas.
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Oda
authors.forename: T
authors.initials: T
authors.lastname: Naka
authors.forename: M
authors.initials: M
authors.lastname: Takeshita
authors.forename: Y
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: M
authors.initials: M
authors.lastname: Tsuneyoshi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000032:analysis; D001859:Bone Neoplasms / Q000737:chemistry / Q000473:pathology*; D002455:Cell Division; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000473:pathology / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000032:analysis*; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D010006:Osteoblasts / Q000473:pathology; D012516:Osteosarcoma / Q000737:chemistry / Q000473:pathology* / Q000556:secondary*; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis*; D014157:Transcription Factors / Q000032:analysis*
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; D019859:Proto-Oncogene Proteins c-met; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins