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Published in: Virchows Archiv 2/2012

01-08-2012 | Original Article

Role of tumor-associated macrophages and angiogenesis in desmoid-type fibromatosis

Authors: Stefhanie Romero, Justyna Szafranska, Eliovel Cabrera, Allan Gonzalez, Ana Peiró, Jaume Llauger, Luis Ortega, Silvia Bague, Belén Canet, Inigo Espinosa, Jaime Prat

Published in: Virchows Archiv | Issue 2/2012

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Abstract

Desmoid-type fibromatosis (DTF) is a rare soft tissue tumor with fibroblastic features affecting two to four individuals per million population per year. Despite its bland microscopic appearance, the tumor behaves aggressively. Although unable to metastasize, DTF tends to recur and local recurrences in anatomically critical sites can be fatal. Tumor-associated macrophages (TAM) play an important role in tumor development through the activation of angiogenesis, particularly in cases of epithelial malignancies. The aim of this study is to investigate the prognostic significance of TAMs and the number of microvessels in DTF. Tumor macrophages (CD163), microvessel density (CD31), and beta-catenin were investigated on 69 primary DTF cases with follow-up information. CTNNB1 mutations were also studied. High density of tumor macrophages and high number of microvessels were associated with a significantly worse recurrence-free survival (P = 0.03 and P = 0.007, respectively). There was a significant correlation between microvessel density and CD163 macrophages (P = 0.02). Furthermore, combination of high number of tumor macrophages and high microvessel density greatly improved the statistical significance (P = 0.000005). Macrophages and microvessels may play an important role in the biologic behavior of DTF. This finding could help in the clinical management of patients with DTF.
Literature
1.
go back to reference Weiss SW, Goldblum JR (2008) Fibromatoses. In: Weiss SW, Goldblum JR (eds) Ezinger and Weiss’s soft tissue tumors, 5th edn. Mosby, Inc, St Louis, pp 227–256 Weiss SW, Goldblum JR (2008) Fibromatoses. In: Weiss SW, Goldblum JR (eds) Ezinger and Weiss’s soft tissue tumors, 5th edn. Mosby, Inc, St Louis, pp 227–256
2.
go back to reference Condeelis J, Pollard JW (2006) Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124(2):263–266PubMedCrossRef Condeelis J, Pollard JW (2006) Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124(2):263–266PubMedCrossRef
3.
go back to reference Lewis CE, Pollard JW (2006) Distinct role of macrophages in different tumor microenvironments. Cancer Res 66(2):605–612PubMedCrossRef Lewis CE, Pollard JW (2006) Distinct role of macrophages in different tumor microenvironments. Cancer Res 66(2):605–612PubMedCrossRef
4.
go back to reference Qian BZ, Pollard JW (2010) Macrophage diversity enhances tumor progression and metastasis. Cell 141(1):39–51PubMedCrossRef Qian BZ, Pollard JW (2010) Macrophage diversity enhances tumor progression and metastasis. Cell 141(1):39–51PubMedCrossRef
5.
go back to reference Frank RE, Saclarides TJ, Leurgans S, Speziale NJ, Drab EA, Rubin DB (1995) Tumor angiogenesis as a predictor of recurrence and survival in patients with node-negative colon cancer. Ann Surg 222(6):695–699PubMedCrossRef Frank RE, Saclarides TJ, Leurgans S, Speziale NJ, Drab EA, Rubin DB (1995) Tumor angiogenesis as a predictor of recurrence and survival in patients with node-negative colon cancer. Ann Surg 222(6):695–699PubMedCrossRef
6.
go back to reference Hollingsworth HC, Kohn EC, Steinberg SM, Rothenberg ML, Merino MJ (1995) Tumor angiogenesis in advanced stage ovarian carcinoma. Am J Pathol 147(1):33–41PubMed Hollingsworth HC, Kohn EC, Steinberg SM, Rothenberg ML, Merino MJ (1995) Tumor angiogenesis in advanced stage ovarian carcinoma. Am J Pathol 147(1):33–41PubMed
7.
go back to reference Olivarez D, Ulbright T, DeRiese W, Foster R, Reister T, Einhorn L, Sledge G (1994) Neovascularization in clinical stage A testicular germ cell tumor: prediction of metastatic disease. Cancer Res 54(10):2800–2802PubMed Olivarez D, Ulbright T, DeRiese W, Foster R, Reister T, Einhorn L, Sledge G (1994) Neovascularization in clinical stage A testicular germ cell tumor: prediction of metastatic disease. Cancer Res 54(10):2800–2802PubMed
8.
go back to reference Weidner N, Carroll PR, Flax J, Blumenfeld W, Folkman J (1993) Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol 143(2):401–409PubMed Weidner N, Carroll PR, Flax J, Blumenfeld W, Folkman J (1993) Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol 143(2):401–409PubMed
9.
go back to reference Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis–correlation in invasive breast carcinoma. N Engl J Med 324(1):1–8PubMedCrossRef Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis–correlation in invasive breast carcinoma. N Engl J Med 324(1):1–8PubMedCrossRef
10.
go back to reference Espinosa I, Edris B, Lee CH, Wei Cheng H, Gilks CB, Wang Y, Montgomery KD, Varma S, Li R, Marinelli RJ, West RB, Nielsen T, Beck AH, van de Rijn M (2011) CSF1 expression in nongynecological leiomyosarcoma is associated with increased tumor angiogenesis. Am J Pathol 179(4):2100–7PubMedCrossRef Espinosa I, Edris B, Lee CH, Wei Cheng H, Gilks CB, Wang Y, Montgomery KD, Varma S, Li R, Marinelli RJ, West RB, Nielsen T, Beck AH, van de Rijn M (2011) CSF1 expression in nongynecological leiomyosarcoma is associated with increased tumor angiogenesis. Am J Pathol 179(4):2100–7PubMedCrossRef
11.
go back to reference Lin EY, Li JF, Gnatovskiy L, Deng Y, Zhu L, Grzesik DA, Qian H, Xue XN, Pollard JW (2006) Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res 66(23):11238–11246PubMedCrossRef Lin EY, Li JF, Gnatovskiy L, Deng Y, Zhu L, Grzesik DA, Qian H, Xue XN, Pollard JW (2006) Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res 66(23):11238–11246PubMedCrossRef
12.
go back to reference Leek RD, Lewis CE, Whitehouse R, Greenall M, Clarke J, Harris AL (1996) Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res 56(20):4625–4629PubMed Leek RD, Lewis CE, Whitehouse R, Greenall M, Clarke J, Harris AL (1996) Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res 56(20):4625–4629PubMed
13.
go back to reference Espinosa I, Jose Carnicer M, Catasus L, Canet B, D'Angelo E, Zannoni GF, Prat J Myometrial invasion and lymph node metastasis in endometrioid carcinomas: tumor-associated macrophages, microvessel density, and HIF1A have a crucial role. Am J Surg Pathol 34 (11):1708-1714 Espinosa I, Jose Carnicer M, Catasus L, Canet B, D'Angelo E, Zannoni GF, Prat J Myometrial invasion and lymph node metastasis in endometrioid carcinomas: tumor-associated macrophages, microvessel density, and HIF1A have a crucial role. Am J Surg Pathol 34 (11):1708-1714
14.
go back to reference Beck AH, Espinosa I, Edris B, Li R, Montgomery K, Zhu S, Varma S, Marinelli RJ, van de Rijn M, West RB (2009) The macrophage colony-stimulating factor 1 response signature in breast carcinoma. Clin Cancer Res 15(3):778–787PubMedCrossRef Beck AH, Espinosa I, Edris B, Li R, Montgomery K, Zhu S, Varma S, Marinelli RJ, van de Rijn M, West RB (2009) The macrophage colony-stimulating factor 1 response signature in breast carcinoma. Clin Cancer Res 15(3):778–787PubMedCrossRef
15.
go back to reference Lee CH, Espinosa I, Vrijaldenhoven S, Subramanian S, Montgomery KD, Zhu S, Marinelli RJ, Peterse JL, Poulin N, Nielsen TO, West RB, Gilks CB, van de Rijn M (2008) Prognostic significance of macrophage infiltration in leiomyosarcomas. Clin Cancer Res 14(5):1423–1430PubMedCrossRef Lee CH, Espinosa I, Vrijaldenhoven S, Subramanian S, Montgomery KD, Zhu S, Marinelli RJ, Peterse JL, Poulin N, Nielsen TO, West RB, Gilks CB, van de Rijn M (2008) Prognostic significance of macrophage infiltration in leiomyosarcomas. Clin Cancer Res 14(5):1423–1430PubMedCrossRef
16.
go back to reference Pritchard DJ, Nascimento AG, Petersen IA (1996) Local control of extra-abdominal desmoid tumors. J Bone Joint Surg Am 78(6):848–854PubMed Pritchard DJ, Nascimento AG, Petersen IA (1996) Local control of extra-abdominal desmoid tumors. J Bone Joint Surg Am 78(6):848–854PubMed
17.
go back to reference Easter DW, Halasz NA (1989) Recent trends in the management of desmoid tumors. Summary of 19 cases and review of the literature. Ann Surg 210(6):765–769PubMedCrossRef Easter DW, Halasz NA (1989) Recent trends in the management of desmoid tumors. Summary of 19 cases and review of the literature. Ann Surg 210(6):765–769PubMedCrossRef
18.
go back to reference McKinnon JG, Neifeld JP, Kay S, Parker GA, Foster WC, Lawrence W Jr (1989) Management of desmoid tumors. Surg Gynecol Obstet 169(2):104–106PubMed McKinnon JG, Neifeld JP, Kay S, Parker GA, Foster WC, Lawrence W Jr (1989) Management of desmoid tumors. Surg Gynecol Obstet 169(2):104–106PubMed
19.
go back to reference Lazar AJ, Tuvin D, Hajibashi S, Habeeb S, Bolshakov S, Mayordomo-Aranda E, Warneke CL, Lopez-Terrada D, Pollock RE, Lev D (2008) Specific mutations in the beta-catenin gene (CTNNB1) correlate with local recurrence in sporadic desmoid tumors. Am J Pathol 173(5):1518–1527PubMedCrossRef Lazar AJ, Tuvin D, Hajibashi S, Habeeb S, Bolshakov S, Mayordomo-Aranda E, Warneke CL, Lopez-Terrada D, Pollock RE, Lev D (2008) Specific mutations in the beta-catenin gene (CTNNB1) correlate with local recurrence in sporadic desmoid tumors. Am J Pathol 173(5):1518–1527PubMedCrossRef
20.
go back to reference Kuhnen C, Helwing M, Rabstein S, Homann HH, Muller KM (2005) Desmoid-type fibromatosis (aggressive fibromatosis). Pathologe 26(2):117–126PubMedCrossRef Kuhnen C, Helwing M, Rabstein S, Homann HH, Muller KM (2005) Desmoid-type fibromatosis (aggressive fibromatosis). Pathologe 26(2):117–126PubMedCrossRef
21.
go back to reference Kubota Y, Takubo K, Shimizu T, Ohno H, Kishi K, Shibuya M, Saya H, Suda T (2009) M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis. J Exp Med 206(5):1089–1102PubMedCrossRef Kubota Y, Takubo K, Shimizu T, Ohno H, Kishi K, Shibuya M, Saya H, Suda T (2009) M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis. J Exp Med 206(5):1089–1102PubMedCrossRef
Metadata
Title
Role of tumor-associated macrophages and angiogenesis in desmoid-type fibromatosis
Authors
Stefhanie Romero
Justyna Szafranska
Eliovel Cabrera
Allan Gonzalez
Ana Peiró
Jaume Llauger
Luis Ortega
Silvia Bague
Belén Canet
Inigo Espinosa
Jaime Prat
Publication date
01-08-2012
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 2/2012
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-012-1265-4

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