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.

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