title: Infiltration of thymidine phosphorylase-positive macrophages is closely associated with tumor angiogenesis and survival in intestinal type gastric cancer.
abstract: Thymidine phosphorylase (TP), an enzyme catalyzing the reversible phospholysis of thymidine, deoxyuridine and their analogs at their respective bases and 2-deoxyribose-1-phosphate, thus promoting angiogenesis, is often expressed in macrophages present in tumor stroma. In this study, we investigated whether infiltration of TP-positive macrophages as well as tumor-associated macrophages affected tumor angiogenesis. TP was expressed in human macrophage-like cells, but not in gastric cancer cells in culture. The expression level of TP, the number of infiltrating CD68+ and CD163+ macrophages, and microvessel density (MVD) in the tumor were further analyzed by immunohistochemistry in 111 patients with gastric cancer. Biostatistical analysis of digitized data obtained by image analysis showed that TP expression was significantly correlated with the number of infiltrating macrophages and MVD in intestinal type gastric cancer (p<0.05). The number of infiltrating macrophages was also correlated with MVD in both the intestinal and diffuse types (p<0.05). An increased number of CD68+ macrophages was significantly associated with poor outcome in patients with intestinal type (p<0.001), but not diffuse type cancer. TP could be a specific marker enzyme that is expressed in tumor-infiltrating macrophages, being associated with tumor angiogenesis and poor prognosis in patients with intestinal-type gastric cancer.
authors.affiliation: Department of Diagnostic Pathology, Kurume University Hospital, Kurume 830-0011, Japan. akihiko4@med.kurume-u.ac.jp
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kawahara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hattori
authors.forename: Jun
authors.initials: J
authors.lastname: Akiba
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Nakashima
authors.forename: Tomoki
authors.initials: T
authors.lastname: Taira
authors.forename: Kosuke
authors.initials: K
authors.lastname: Watari
authors.forename: Fumihito
authors.initials: F
authors.lastname: Hosoi
authors.forename: Manami
authors.initials: M
authors.lastname: Uba
authors.forename: Yuji
authors.initials: Y
authors.lastname: Basaki
authors.forename: Kikuo
authors.initials: K
authors.lastname: Koufuji
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shirouzu
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Akiyama
authors.forename: Michihiko
authors.initials: M
authors.lastname: Kuwano
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kage
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ono
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002277:Carcinoma / Q000098:blood supply / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D013274:Stomach Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000401:mortality* / Q000556:secondary; D016019:Survival Analysis; D013939:Thymidine Phosphorylase / Q000378:metabolism*; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D011956:Receptors, Cell Surface; D013939:Thymidine Phosphorylase; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C543750:TYMP protein, human