title: Macrophage expression of tartrate-resistant acid phosphatase as a prognostic indicator in colon cancer.
abstract: Recent research has indicated that separate populations of macrophages are associated with differing outcomes in cancer survival. In our study, we examine macrophage expression of tartrate-resistant acid phosphatase (TRAP) and its effect on survival in colon cancer. Immunohistochemical analysis on colorectal adenocarcinomas confirmed macrophage expression of TRAP. Co-localization of TRAP with CD68, a pan-macrophage marker, revealed that TRAP is present in some but not all sub-populations of macrophages. Further co-localization of TRAP with CD163, an M2 marker, revealed that TRAP is expressed by both M2 and non-M2 macrophages. TRAP expression was then measured using the AQUA method of quantitative immunofluorescence in a tissue microarray consisting of 233 colorectal cancer patients seen at Yale-New Haven Hospital. Survival analysis revealed that patients with high TRAP expression have a 22 % increase in 5-year survival (uncorrected log-rank p = 0.025) and a 47 % risk reduction in disease-specific death (p = 0.02). This finding was validated in a second cohort of older cases consisting of 505 colorectal cancer patients. Patients with high TRAP expression in the validation set had a 19 % increase in 5-year survival (log-rank p = 0.0041) and a 52 % risk reduction in death (p = 0.0019). These results provide evidence that macrophage expression of TRAP is associated with improved outcome and implicates TRAP as a potential biomarker in colon cancer.
authors.affiliation: Department of Pathology, BML 116, Yale University Medical School, 310 Cedar St., PO Box 208023, New Haven, CT, 06520-8023, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: How
authors.forename: Jason R
authors.initials: JR
authors.lastname: Brown
authors.forename: Sasha
authors.initials: S
authors.lastname: Saylor
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
mesh_terms: D000135:Acid Phosphatase / Q000096:biosynthesis*; D000230:Adenocarcinoma / Q000401:mortality* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D014408:Biomarkers, Tumor; D003110:Colonic Neoplasms / Q000401:mortality* / Q000473:pathology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis*; D008264:Macrophages / Q000145:classification / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D055815:Young Adult; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D000135:Acid Phosphatase; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D007527:Isoenzymes; D011956:Receptors, Cell Surface; D000071681:Tartrate-Resistant Acid Phosphatase; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule