title: B7-H3 expression in colorectal cancer: nuclear localization strongly predicts poor outcome in colon cancer.
abstract: In colorectal cancer there is a need for molecular markers that can complement the histopathological staging in predicting the likelihood of disease recurrence following curatively intended surgery. B7-H3 is an immunoregulatory protein shown to be overexpressed in several cancer forms, often associated with more advanced disease and poor prognosis. We wanted to examine whether B7-H3 could be a potential prognostic marker in colorectal cancer. Paraffin-embedded samples from 277 colorectal cancer patients were immunostained with anti-B7-H3 antibody. B7-H3 was expressed in the tumor cell cytoplasm and cell membrane in 62% and 46% of the samples, respectively. Unexpectedly, B7-H3 was expressed in the nucleus in 30% of the tumors. The nuclear localization was confirmed by Western immunoblotting of subcellular fractions. Importantly, in colon cancer, nuclear B7-H3 expression was independently and significantly associated with reduced metastasis-free, disease-specific and overall survival. B7-H3 expression in tumor-associated vasculature and fibroblasts was observed in the majority of samples, and endothelial B7-H3 expression was also significantly associated with poor outcome in colon cancer. In rectal cancer patients, the only significant association was between fibroblast B7-H3 expression and shorter metastasis-free survival. Few significant associations to clinicopathological parameters were seen. The results indicate that nuclear B7-H3 might be involved in colon cancer progression and metastasis, and suggest that nuclear B7-H3 could become a useful prognostic marker in colon cancer.
authors.affiliation: Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. vibing@rr-research.no
authors.forename: Vibeke Anett
authors.initials: VA
authors.lastname: Ingebrigtsen
authors.forename: Kjetil
authors.initials: K
authors.lastname: Boye
authors.forename: Christina
authors.initials: C
authors.lastname: Tekle
authors.forename: Jahn Martin
authors.initials: JM
authors.lastname: Nesland
authors.forename: Kjersti
authors.initials: K
authors.lastname: Flatmark
authors.forename: Oystein
authors.initials: O
authors.lastname: Fodstad
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060887:B7 Antigens / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D055815:Young Adult
chemical_list: D060887:B7 Antigens; D014408:Biomarkers, Tumor; C423237:CD276 protein, human