Am J Cancer Res 2013;3(5): 523-529
Original Article
Association between tumor-associated macrophage infiltration, high grade
prostate cancer, and biochemical recurrence after radical prostatectomy
Kiran Gollapudi, Colette Galet, Tristan Grogan, Hong Zhang, Jonathan W Said, Jiaoti Huang, David Elashoff, Stephen J
Freedland, Matthew Rettig, William J Aronson
Department of Urology, School of Medicine, University of California-Los Angeles, Los Angeles, California; Department of
Medicine Statistics Core, School of Medicine, University of California-Los Angeles, Los Angeles, California; Department of
Pathology, School of Medicine, University of California-Los Angeles, Los Angeles, Californiad; Department of Surgery, Durham
Veterans Affairs Medical Center and Division of Urologic Surgery and Duke Prostate Center, Departments of Surgery and
Pathology, Duke University Medical Center, Durham, Nce; Division of Hematology/Oncology, Department of Medicine, VA Greater
Los Angeles Healthcare System, Los Angeles, California; Urology Section, Department of Surgery, VA Greater Los Angeles
Healthcare System, Los Angeles, California; Dr Zhang’s current affiliation: Department of Pathology, Anhui Medical University,
Hefei, Anhui Province, P.R China
Received July 31, 2013; Accepted September 3, 2013; Epub November 1, 2013; Published November 15, 2013
Abstract: Background: Tumor-associated macrophages (TAMs) are a key component of the inflammatory microenvironment.
Their role in prostate cancer development and progression remains unclear. We examined whether the amount of TAMs in
prostate cancer is: 1) higher than prostatic intraepithelial neoplasia (PIN) and benign tissue 2) associated with poorly
differentiated disease, and 3) predictive of biochemical recurrence among surgically treated men. Methods: A tissue microarray
(TMA) of prostatectomy specimens from 332 patients was stained for CD68, a TAM marker. A separate TMA was used for
validation. Associations between mean TAMs in cancer cores and PSA recurrence were determined by Cox proportional hazards
models after adjusting for age, preoperative PSA, race, body mass index, pathologic Gleason sum, seminal vesicle invasion,
extracapsular extension, and margin status. Results: Mean TAM number was higher in cancer versus PIN and benign tissue
(p<0.0001). Mean TAM number was higher in Gleason grade 4 cores vs. Gleason grade 3 cores (p=0.003). On multivariable
analysis, no association was observed between mean TAM number per cancer core and biochemical recurrence in either
cohort. Conclusion: Mean TAM number was higher in cancer cores vs. PIN and benign tissue, and higher in high grade prostate
cancer supporting the potential role of TAMs in prostate cancer development. However, TAMs were not associated with
biochemical recurrence after radical prostatectomy suggesting TAM counts do not provide independent prognostic value among
surgically treated men. Further studies are required to elucidate the functional significance of TAMs in the prostate cancer
microenvironment. (ajcr0000221).
Keywords: Biochemical recurrence, cancer development, prostate, tumor associated macrophages, tissue microarray
Address correspondence to: Dr. William J Aronson or Kiran Gollapudi, Department of Urology, School of Medicine, University of
California-Los Angeles, Box 951738, Los Angeles, California 90095-1738. Tel: 310-268-3446; Fax: 310-268-4858; E-mail:
waronson@ucla.edu (WJA); kgollapudi@mednet.ucla.edu (KG)
Original Article
Association between tumor-associated macrophage infiltration, high grade
prostate cancer, and biochemical recurrence after radical prostatectomy
Kiran Gollapudi, Colette Galet, Tristan Grogan, Hong Zhang, Jonathan W Said, Jiaoti Huang, David Elashoff, Stephen J
Freedland, Matthew Rettig, William J Aronson
Department of Urology, School of Medicine, University of California-Los Angeles, Los Angeles, California; Department of
Medicine Statistics Core, School of Medicine, University of California-Los Angeles, Los Angeles, California; Department of
Pathology, School of Medicine, University of California-Los Angeles, Los Angeles, Californiad; Department of Surgery, Durham
Veterans Affairs Medical Center and Division of Urologic Surgery and Duke Prostate Center, Departments of Surgery and
Pathology, Duke University Medical Center, Durham, Nce; Division of Hematology/Oncology, Department of Medicine, VA Greater
Los Angeles Healthcare System, Los Angeles, California; Urology Section, Department of Surgery, VA Greater Los Angeles
Healthcare System, Los Angeles, California; Dr Zhang’s current affiliation: Department of Pathology, Anhui Medical University,
Hefei, Anhui Province, P.R China
Received July 31, 2013; Accepted September 3, 2013; Epub November 1, 2013; Published November 15, 2013
Abstract: Background: Tumor-associated macrophages (TAMs) are a key component of the inflammatory microenvironment.
Their role in prostate cancer development and progression remains unclear. We examined whether the amount of TAMs in
prostate cancer is: 1) higher than prostatic intraepithelial neoplasia (PIN) and benign tissue 2) associated with poorly
differentiated disease, and 3) predictive of biochemical recurrence among surgically treated men. Methods: A tissue microarray
(TMA) of prostatectomy specimens from 332 patients was stained for CD68, a TAM marker. A separate TMA was used for
validation. Associations between mean TAMs in cancer cores and PSA recurrence were determined by Cox proportional hazards
models after adjusting for age, preoperative PSA, race, body mass index, pathologic Gleason sum, seminal vesicle invasion,
extracapsular extension, and margin status. Results: Mean TAM number was higher in cancer versus PIN and benign tissue
(p<0.0001). Mean TAM number was higher in Gleason grade 4 cores vs. Gleason grade 3 cores (p=0.003). On multivariable
analysis, no association was observed between mean TAM number per cancer core and biochemical recurrence in either
cohort. Conclusion: Mean TAM number was higher in cancer cores vs. PIN and benign tissue, and higher in high grade prostate
cancer supporting the potential role of TAMs in prostate cancer development. However, TAMs were not associated with
biochemical recurrence after radical prostatectomy suggesting TAM counts do not provide independent prognostic value among
surgically treated men. Further studies are required to elucidate the functional significance of TAMs in the prostate cancer
microenvironment. (ajcr0000221).
Keywords: Biochemical recurrence, cancer development, prostate, tumor associated macrophages, tissue microarray
Address correspondence to: Dr. William J Aronson or Kiran Gollapudi, Department of Urology, School of Medicine, University of
California-Los Angeles, Box 951738, Los Angeles, California 90095-1738. Tel: 310-268-3446; Fax: 310-268-4858; E-mail:
waronson@ucla.edu (WJA); kgollapudi@mednet.ucla.edu (KG)
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American Journal of Cancer Research
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