title: Osteopontin induced by macrophages contribute to metachronous liver metastases in colorectal cancer.
abstract: Even after radical surgery for stage II and stage III colorectal cancer, metachronous liver metastasis is frequently observed. The aim of this study was to identify the risk of metachronous liver metastasis with retrospective clinicopathological study. Immunohistochemistry was performed  to evaluate the expression of Osteopontin (OPN), CD-68, and CD105 in 41 cases of stage II and stage III colorectal cancer tissue. Stage II and stage III colorectal cancer patients who had undergone R0 resection were classified into two groups: with metachronous liver metastasis (m-LM; n =  17) and without liver metastases (control; n = 24). Additionally, double-immunofluorescence staining was performed using antibodies to OPN and CD68. OPN-positive cells were frequently colocalized with CD68 immunoreactivity. OPN and microvascular density expression in the central area were  significantly higher in the m-LM (OPN; control 4.3 ± 0.56, m-LV 10.8 ± 1.48, P < 0.05; microvascular density control 18.5 ± 2.86, m-LV 31.4 ± 4.39, P < 0.05), while CD68 expression in the invasive margin was significantly higher in the control  group (control 98.9 ± 7.31, m-LV 28.2 ± 3.18, P < 0.05). These results suggest that the risk of metachronous liver metastasis could be well predicted by immunohistochemical staining of OPN in the central areas, and CD68 in the invasive margins of tumors.
authors.affiliation: Department of Surgery, Kinki University Faculty of Medicine, Ohno-Higashi Osaka-Sayama, Osaka, Japan. imano@med.kindai.ac.jp
authors.forename: Motohiro
authors.initials: M
authors.lastname: Imano
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Okuno
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Itoh
authors.forename: Takao
authors.initials: T
authors.lastname: Satou
authors.forename: Eizaburo
authors.initials: E
authors.lastname: Ishimaru
authors.forename: Takushi
authors.initials: T
authors.lastname: Yasuda
authors.forename: Jin-Ichi
authors.initials: J
authors.lastname: Hida
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Imamoto
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Takeyama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shiozaki
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000556:secondary* / Q000601:surgery; D018450:Disease Progression; D000071063:Endoglin; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D053495:Osteopontin / Q000096:biosynthesis*; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D000071063:Endoglin; D053495:Osteopontin; D011956:Receptors, Cell Surface; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C064206:ENG protein, human