title: Expression of osteopontin and HGF/met in adult soft tissue tumors.
abstract: There is a need for molecular markers that predict biological behavior of adult soft tissue tumors. Elevated levels of osteopontin (OPN) a transformation-linked protein, have been associated with poor survival in many cancers. OPN induces cell migration in cancer cells, in part through activation of the hepatocyte growth factor (HGF) receptor (Met) and its signaling pathway. Met expression has been associated with a poor prognosis in some sarcomas. In a series of 15 patients with adult soft tissue tumors, we found that mRNA levels of OPN (p=0.015), Met (p=0.03) and HGF (p<0.001) were significantly higher in tumor tissues relative to paired normal tissues. By immunohistochemistry, in tumor tissue from 33 patients, we demonstrated that increased expression of OPN, but not Met protein, was associated with higher stage (p=0.025) and grade (p=0.005). We found that increased expression of OPN, but not Met protein, was associated with decreased overall survival (p=0.008) at five years. This study, which is the first to examine coexpression of these two markers, suggests that OPN may have potential as a prognostic marker in adult soft tissue sarcomas, and further that OPN+/-Met signaling pathways may contribute to their biological behavior.
authors.affiliation: London Regional Cancer Program and Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.
authors.forename: Vivien H C
authors.initials: VH
authors.lastname: Bramwell
authors.forename: Alan B
authors.initials: AB
authors.lastname: Tuck
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Wilson
authors.forename: Larry W
authors.initials: LW
authors.lastname: Stitt
authors.forename: Anil K
authors.initials: AK
authors.lastname: Cherian
authors.forename: Stewart C
authors.initials: SC
authors.lastname: Rorke
authors.forename: Waleed
authors.initials: W
authors.lastname: Al-Katib
authors.forename: Carl O
authors.initials: CO
authors.lastname: Postenka
authors.forename: Ann F
authors.initials: AF
authors.lastname: Chambers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D053495:Osteopontin; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*; D012983:Soft Tissue Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met