title: Type and location of tumor-infiltrating macrophages and lymphatic vessels predict survival of colorectal cancer patients.
abstract: The type of tumor-infiltrating macrophages may be decisive in tumor immunity, lymphangiogenesis and in the clinical outcome of cancer. Here, we elucidated the prognostic significance of lymphatic vessels, different types of macrophages and the balance between different macrophage types in colorectal cancer. We analyzed the impact of density, type and location of macrophages on the clinical behavior of 159 primary colorectal carcinomas using CD68 as a pan-macrophage marker and CLEVER-1/Stabilin-1 as a marker for regulatory/suppressive macrophages. Podoplanin was used as a pan-lymphatic vessel marker. A high number of CLEVER-1/Stabilin-1(+)  peritumoral macrophages positively correlated with survival (p = 0.04). However, in more advanced disease (Stage IV), the patients with a high number of peritumoral or intratumoral CLEVER-1/Stabilin-1(+)  macrophages had a shorter disease-specific survival (p = 0.05, and p = 0.008, respectively). Moreover, a low number of suppressive intratumoral CLEVER-1/Stabilin-1(+)  macrophages among high numbers of CD68(+)  macrophages correlated with a low number of distant recurrences (p = 0.01) and to fewer disease relapses exclusively in the liver as well (p = 0.006). A high number of intratumoral lymphatics correlated with poor survival (p = 0.03). The results of this work suggest that the type of macrophages, number of lymphatic vessels and their location contribute to the clinical behavior of colorectal cancer in a disease stage-specific manner.
authors.affiliation: Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland.
authors.forename: Annika
authors.initials: A
authors.lastname: Algars
authors.forename: Heikki
authors.initials: H
authors.lastname: Irjala
authors.forename: Samuli
authors.initials: S
authors.lastname: Vaittinen
authors.forename: Heikki
authors.initials: H
authors.lastname: Huhtinen
authors.forename: Jari
authors.initials: J
authors.lastname: Sundström
authors.forename: Marko
authors.initials: M
authors.lastname: Salmi
authors.forename: Raija
authors.initials: R
authors.lastname: Ristamäki
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D042601:Lymphatic Vessels / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D016019:Survival Analysis; D000098853:Podoplanin
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D008562:Membrane Glycoproteins; D016201:Receptors, Lymphocyte Homing; C117468:PDPN protein, human; D000098853:Podoplanin; C449926:STAB1 protein, human