Date of Award
January 2015
Document Type
Open Access Thesis
Degree Name
Medical Doctor (MD)
Department
Medicine
First Advisor
David L. Rimm
Subject Area(s)
Pathology
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 subpopulations 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 for
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 of death (p=0.0019). TRAP expression was also significantly associated
with brisk rather than non-brisk tumor-infiltrating lymphocytes. These results provide
evidence that macrophage expression of TRAP is associated with improved outcome, and
implicates TRAP as a potential biomarker in colon cancer.
Recommended Citation
How, Chi-Joan, "Tartrate-Resistant Acid Phosphatase: Prognosis In Colorectal Cancer And The M1/m2 Distinction." (2015). Yale Medicine Thesis Digital Library. 1979.
https://elischolar.library.yale.edu/ymtdl/1979
Comments
This is an Open Access Thesis.