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Sarcoma spreads primarily through the vascular system: are there biomarkers associated with vascular spread?

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Abstract

Sarcomas are a heterogeneous group of tumors with specific molecular characteristics and currently classified on the basis of their tissue of origin and histologic appearance. Except for epithelioid sarcoma, clear cell sarcoma, angiosarcoma and rhabdomyosarcoma, which may spread to regional lymph nodes, the other histotypes spread via the vascular system to the lungs most of the time. A variety of molecular approaches, including gene expression profiling, have identified candidate biomarkers and generated insights into sarcoma biology. The comprehension of the pathogenesis of this malignancy according to the mesenchymal stem cell hypothesis parallels the description of several molecular pathways deregulated in sarcoma. Individuation of vascular spread biomarkers is actually focused on the study of factors involved both in hemostasis and angiogenesis. Interestingly the microenvironment of sarcomas showed the very same mesenchymal origin of the surrounding stromal cells. The presence of circulating tumor cells and miRNAs in blood samples of sarcoma patients represents the possibility not only to better stratify patients group according to the prognosis but also to tailor new individualized therapy. So, it could be predicted that some genes expressed in a specific sarcoma might have prognostic significance or therapeutic targeting potential and molecular targets can be identified in the tumor or in the tumor microenvironment. Therefore the initial evaluation of a sarcoma patient should include in-depth genetic evaluation including karyotyping and c-DNA/protein expression profiling. The chemokine signaling demonstrated to be deeply implicated in sarcoma development as well as to have a significant role in development of metastatic disease, especially in directing tumor cells towards the preferential sites of metastases in sarcoma, lung and bone. It is unsolved if the blood stream is a more favorable environment compared to lymphatic or if lymph nodes are more efficient in destroying metastatic sarcoma cells. But the comprehension of the regulatory mechanisms of the behavior of mesenchymal malignant tumors is at its dawn.

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References

  1. Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2:563–572

    Article  PubMed  CAS  Google Scholar 

  2. Nguye DX, Bos PD, Massague J (2009) Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer 9:274–284

    Article  Google Scholar 

  3. Psaila B, Lyden D (2009) The metastatic niche: adapting the foreign soil. Nat Rev Cancer 9:285–293

    Article  PubMed  CAS  Google Scholar 

  4. Paget S (1889) The distribution of secondary growths in cancer of the breast. Lancet 1:571–573

    Article  Google Scholar 

  5. Paget S (1989) The distribution of secondary growths in cancer of the breast. Cancer Metastasis Rev 8:98–101

    PubMed  CAS  Google Scholar 

  6. Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, Zhu Z, Hicklin D, Wu Y, Port JL, Altorki N, Port ER, Ruggero D, Shmelkov SV, Jensen KK, Rafii S, Lyden D (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438(7069):820–827

    Article  PubMed  CAS  Google Scholar 

  7. MackalL CL, Meltzer PS, Helman LJ (2002) Focus on sarcomas. Cancer Cell 2(3):175–178

    Article  PubMed  CAS  Google Scholar 

  8. Jl Tolar et al (2007) Sarcoma derived from cultured mesenchymal cells. Stem Cells 25(2):371–379

    Article  Google Scholar 

  9. Helman LJ, Meltzer P (2003) Mechanisms of sarcoma development. Nat Rev Cancer 3:685–694

    Article  PubMed  CAS  Google Scholar 

  10. Fletcher CDM, Unni KK, Mertens F et al (2002) Pathology and genetics of tumours of soft tissue and bone. IARC Press, Lyon

    Google Scholar 

  11. Eilber FC, Dry SM (2008) Diagnosis and management of synovial sarcoma. J Surg Oncol 97:314–320

    Article  PubMed  Google Scholar 

  12. Clark J, Rocques PJ, Crew AJ et al (1994) Identification of novel genes, SYT and SSX, involved in the t(X;18)(p11.2;q11.2) translocation found in human synovial sarcoma. Nat Genet 7:502–508

    Article  PubMed  CAS  Google Scholar 

  13. Kawai A, Woodruff J, Healey JH et al (1998) SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma. N Engl J Med 338:153–160

    Article  PubMed  CAS  Google Scholar 

  14. Sandberg AA, Bridge JA (2002) Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors. Synovial sarcoma. Cancer Genet Cytogenet 133:1–23

    Article  PubMed  CAS  Google Scholar 

  15. Henderson SR, Guiliano D, Presneau N et al (2005) A molecular map of mesenchymal tumors. Genome Biol 6:R76

    Article  PubMed  Google Scholar 

  16. Kawai A, Kondo T, Suehara Y, Kikuta K, Hirohashi S (2008) Global protein-expression analysis of bone and soft tissue sarcomas. Clin Orthop Relat Res 466(9):2099–2106

    Article  PubMed  Google Scholar 

  17. Ladany M, Wodruff JM, Scheithauer BW, Bridge JA, Barr FG et al (2001) Letter to editor. Re: O’Sullivan MJ, Kyriakos M, Zhu X, Wick MR, Swanson PE, Dehner LP, Humphrey PA, Pfeifer JD (2000) Malignant peripheral nerve sheath tumor with t(X;18) : a pathologic and molecular study. Mod Pathol 13:1336–1446. Mod Pathol 14(7):733–737

  18. Lubieniecka JM, de Bruijn DR, Su L et al (2008) Histone deacetylase inhibitors reverse SS18-SSX-mediated polycomb silencing of the tumor suppressor early growth response 1 in synovial sarcoma. Cancer Res 68:4303–4310

    Article  PubMed  CAS  Google Scholar 

  19. Fernebro J, Francis P, Eden P et al (2006) Gene expression profiles relate to SS18/SSX fusion type in synovial sarcoma. Int J Cancer 118:1165–1172

    Article  PubMed  CAS  Google Scholar 

  20. Subramanian S, Lui WO, Lee CH et al (2008) Micro-RNA expression signature of human sarcomas. Oncogene 27(14):2015–2026

    Article  PubMed  CAS  Google Scholar 

  21. Dela Cruz F, Matushansky I (2011) MicroRNAs in chromosomal translocation-associated solid tumors: learning from sarcomas. Discov Med 12(65):307–317

    PubMed  Google Scholar 

  22. Nielsen TO, West RB, Linn SC et al (2002) Molecular characterisation of soft tissue tumours: a gene expression study. Lancet 359:1301–1307

    Article  PubMed  CAS  Google Scholar 

  23. Ray-Coquard I, Le Cesne A, Whelan JS et al (2008) A phase II study of gefitinib for patients with advanced HER-1 expressing synovial sarcoma refractory to doxorubicin-containing regimens. Oncologist 13:467–473

    Article  PubMed  CAS  Google Scholar 

  24. Fletcher CD, Gustafson P, Rydholm A et al (2001) Clinicopathologic re-evaluation of 100 malignant fibrous histiocytomas; prognostic relevance of subclassification. J Clin Oncol 19:3045–3050

    PubMed  CAS  Google Scholar 

  25. Beck AH, West RB, van de Rijn M (2010) Gene expression profiling for the investigation of soft tissue sarcoma pathogenesis and the identification of diagnostic, prognostic and predictive biomarkers. Virchows Arch 456:141–151

    Article  PubMed  CAS  Google Scholar 

  26. Hernando E, Charytonowicz E, Dudas ME, Menendez S, Matushansky I, Mills J, Socci ND, Behrendt N, Ma L, Maki RG, Pandolfi PP, Cordon-Cardo C (2007) The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas. Nat Med 13:748–753

    Article  PubMed  CAS  Google Scholar 

  27. Lee YF, John M, Edwards S et al (2003) Molecular classification of synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas by gene expression profiling. Br J Cancer 88:510–515

    Article  PubMed  CAS  Google Scholar 

  28. Lee CH, Espinosa I, Vrijaldenhoven S et al (2008) Prognostic significance of macrophage infiltration in leiomyosarcomas. Clin Cancer Res 14:1423–1430

    Article  PubMed  CAS  Google Scholar 

  29. Sorbye SW, Kilvaer T, Valkov A, Donnem T, Smeland E, Al-Shibli K, Bremnes RM, Busund LT (2011) Prognostic impact of lymphocytes in soft tissue sarcomas. PLoS ONE 6(1):e14611

    Article  PubMed  Google Scholar 

  30. Pedeutour F, Forus A, Coindre JM, Berner JM, Nicolo G, Michiels JF et al (1999) Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors. Genes Chromosomes Cancer 24:30–34

    Google Scholar 

  31. Fritz B, Schubert F, Wrobel G, Schwaenen C, Wessendorf S, Nessling M et al (2002) Microarray-based copy number and expression profiling in dedifferentiated and pleomorphic liposarcomas. Cancer Res 62:2993–2998

    PubMed  CAS  Google Scholar 

  32. Baird K, Davis S, Antonescu CR et al (2005) Gene expression profiling of human sarcomas: insights into sarcoma biology. Cancer Res 65:9226–9235

    Article  PubMed  CAS  Google Scholar 

  33. Francis P, Namlos HM, Muller C et al (2007) Diagnostic and prognostic gene expression signatures in 177 soft tissue sarcomas: hypoxia-induced transcription profile signifies metastatic potential. BMC Genomics 8:73

    Article  PubMed  Google Scholar 

  34. Singer S, Socci ND, Ambrosini G et al (2007) Gene expression profiling of liposarcoma identifies distinct biological types/subtypes and potential therapeutic targets in well-differentiated and dedifferentiated liposarcoma. Cancer Res 67:6626–6636

    Article  PubMed  CAS  Google Scholar 

  35. Ugras S, Brill E, Jacobsen A, Hafner M, Socci ND, Decarolis PL, Khanin R, O’Connor R, Mihailovic A, Taylor BS, Sheridan R, Gimble JM, Viale A, Crago A, Antonescu CR, Sander C, Tuschl T, Singer S (2011) Small RNA sequencing and functional characterization reveals MicroRNA-143 tumor suppressor activity in liposarcoma. Cancer Res 71(17):5659–5669

    Article  PubMed  CAS  Google Scholar 

  36. Carneiro A, Francis P, Bendahl PO, Fernebro J, Akerman M, Fletcher C, Rydholm A, Borg A, Nilbert M. Indistinguishable genomic profiles and shared prognostic markers in undifferentiated pleomorphic sarcoma and leiomyosarcoma: different sides of a single coin? Lab Invest. 2009 Jun;89(6):668-675. Erratum in: Lab Invest (2009) 89(7):840

    Google Scholar 

  37. Matushansky I, Hernando E, Socci ND, Mills JE, Matos TA, Edgar MA, Singer S, Maki RG, Cordon-Cardo C (2007) Derivation of sarcomas from mesenchymal stem cells via inactivation of the Wnt pathway. J Clin Invest. 117(11):3248–3257

    Article  PubMed  CAS  Google Scholar 

  38. Linn SC, West RB, Pollack JR, Zhu S, Hernandez-Boussard T, Nielsen TO, Rubin BP, Patel R, Goldblum JR, Siegmund D, Botstein D, Brown PO, Gilks CB, van de Rijn M (2003) Gene expression patterns and gene copy number changes in dermatofibrosarcoma protuberans. Am J Pathol 163(6):2383–2395

    Article  PubMed  CAS  Google Scholar 

  39. Abbott JJ, Erickson-Johnson M, Wang X, Nascimento AG, Oliveira AM (2006) Gains of COL1A1-PDGFB genomic copies occur in fibrosarcomatous transformation of dermatofibrosarcoma protuberans. Mod Pathol 19(11):1512–1518

    PubMed  CAS  Google Scholar 

  40. McArthur G (2007) Dermatofibrosarcoma protuberans: recent clinical progress. Ann Surg Oncol 14(10):2876–2886

    Article  PubMed  Google Scholar 

  41. Lips DJ, Barker N, Clevers H, Hennipman A (2009) The role of APC and beta-catenin in the aetiology of aggressive fibromatosis (desmoid tumors). Eur J Surg Oncol 35(1):3–10

    Article  PubMed  CAS  Google Scholar 

  42. Leong SP, Cady B, Jablons DM, Garcia-Aguilar J, Reintgen D, Jakub J, Pendas S, Duhaime L, Cassell R, Gardner M, Giuliano R, Archie V, Calvin D, Mensha L, Shivers S, Cox C, Werner JA, Kitagawa Y, Kitajima M (2006) Clinical patterns of metastasis. Cancer Metastasis Rev 25(2):221–232

    Article  PubMed  Google Scholar 

  43. Billingsley KG, Burt ME, Jara E, Ginsberg RJ, Woodruff JM, Leung DH, Brennan MF (1999) Pulmonary metastases from soft tissue sarcoma: Analysis of patterns of diseases and post metastasis survival. Ann Surg 229(5):602–610 discussion 610–612

    Article  PubMed  CAS  Google Scholar 

  44. Sahai E (2007) Illuminating the metastatic process. Nat Rev Cancer 7:737–749

    Article  PubMed  CAS  Google Scholar 

  45. Sleeman JP, Nazarenko I, Thiele W (2011) Do all roads lead to Rome? Routes to metastasis development. Int J Cancer 128(11):2511–2526

    Article  PubMed  CAS  Google Scholar 

  46. Kasthuri RS, Taubman MB, Mackman N (2009) Role of tissue factor in Cancer. JCO 27(29):4834–4838

    Article  CAS  Google Scholar 

  47. Kilvaer TK, Valkov A, Sorbye S, Smeland E, Bremnes RM, Busund LT, Donnem T (2010) Profiling of VEGFs and VEGFR sas prognostic factors in soft tissue sarcoma: VEGFR-3 is an independent predictor of poor prognosis. PLoS One 5(12):e15368

    Article  PubMed  CAS  Google Scholar 

  48. Kalen M, Heikura T, Karvinen H, Nitzsche A, Weber H, Esser N, Yla-Herttuala S, Hellstrom M (2011) Gamma-secretase inhibitor treatment promotes VEGF-A driven blood vessel growth and vascular leakage but disrupts neovascular perfusion. PLoS ONE 6(4):e18709

    Article  PubMed  CAS  Google Scholar 

  49. Bray SJ (2006) Notch signalling: a simple pathway becomes complex. Nat Rev 7:678–689

    Article  CAS  Google Scholar 

  50. Leong SPL, Nakakura EK, Pollock R, Chot MA, Morton DL, Henner WD, Lal A, Pillai R, Clark OH, Bacy B (2010) Unique patterns of metastases in common and rare types of malignancy. JCO 103:607–614

    Google Scholar 

  51. He C, Xiong J, Xu X, Lu W, Liu L, Xiao D, Wang D (2009) Functional elucidation of MiR-34 in osteosarcoma cells and primary tumor samples. Biochem Biophys Res Commun 388(1):35–40

    Article  PubMed  CAS  Google Scholar 

  52. Song B, Wang Y, Xi Y et al (2009) Mechanism of chemoresistance mediated by miT-140 in human osteosarcoma and conon cancer cells. Oncogene 28(46):4065–4074

    Article  PubMed  CAS  Google Scholar 

  53. Song B, Wang Y et al (2010) Molecular mechanism of chemoresistence by miR-125 in osteosarcoma and colon cancer cells. Mol Cancer 30(9):96

    Article  Google Scholar 

  54. Zang J, Guo W, Yang RL, Tang XD, Ji T (2010) Ewing ‘s sarcoma of bone: treatment results and prognostic factors. Zhonghua Wai Ke Za Zhi 48(12):896–899

    PubMed  Google Scholar 

  55. Lulla RR, Costa FF, Bischof JM, Chou PM, de Bonaldo M, Vanin EF, Soares MB (2011) Identification of differentially expressed micro-RNAs in osteosarcoma. Sarcoma 2011(6):1–6

    Article  Google Scholar 

  56. Bianchi F, Nicassio F, Marzi M et al (2011) A serum circulating miRNA diagnostic test to identify asymptomatic high-risk individuals with early stage lung cancer. EMBO Mol Med 3(8):495–503

    Article  PubMed  CAS  Google Scholar 

  57. Matushansky I, Charytonowicz E, Mills J, Siddiqi S, Hricik T, Cordon-Cardo C (2009) MFH classification: differentiating undifferentiated pleomorphic sarcoma in the 21st Century. Expert Rev Anticancer Ther 9(8):1135–1144

    Article  PubMed  CAS  Google Scholar 

  58. Camp RK, Neumeister V, Rimm DL (2008) A decade of tissue microarrays: progress in the discovery and validation of cancer biomarkers. J Clin Oncol 26:5630–5637

    Article  PubMed  Google Scholar 

  59. Dubois SG, Epling CL, Teague J, Matthay KK, Sinclair E (2010) Flow cytometric detection of Ewing sarcoma cells in peripheral blood and bone marrow. Pediatr Blood Cancer 54(1):13–18

    Article  PubMed  Google Scholar 

  60. Nakanishi H, Myoui A, Ochi T, Aozasa K (1997) P-glycoprotein expression in soft-tissue sarcomas. J Cancer Res Clin Oncol 123:352–356

    PubMed  CAS  Google Scholar 

  61. Wurl P, Meye A, Schmidt H et al (1998) High prognostic significance of MdM2/p53 co-overexpression in soft-tissue sarcomas of the extremities. Oncogene 16:1183–1185

    Article  PubMed  CAS  Google Scholar 

  62. Kaway A, Noguchi M et al (1994) Nuclear immunoreaction of p %£ protein in soft tissue sarcomas. A possible prognostic factor. Cancer 73:2499–2505

    Article  Google Scholar 

  63. Taubert H, Meye A, Wurl P (1996) Prognosis is correlated with p53 mutation type for soft tissue sarcoma patients. Cancer Res 56:4134–4136

    PubMed  CAS  Google Scholar 

  64. Konomoto T, Fukuda T, Hayashi K, Kumazawa J, Tsuneyoshi M (1998) Leyomiosarcoma in soft tissue: examination of p53 status and cell proliferating factors in different locations. Human Pathol 29:74–81

    Article  CAS  Google Scholar 

  65. Antonescu CR, Leung DH et al (2000) Alterations of cell cycle regulators in localized synovial sarcoma: a multifactorial study with prognostic implications. Am J Pathol 156:977–983

    Article  PubMed  CAS  Google Scholar 

  66. Taubert H, Koehler T et al (2000) mdm2 mRNA level is a prognostic factor in soft tissue sarcoma. Mol Med 6:50–59

    PubMed  CAS  Google Scholar 

  67. Oda Y, Sakamoto A, Saito T et al (2000) Expression of hepatocyte growth factor (HGF)/scatter factor and its receptor c-MET correlates with poor prognosis in synovial sarcoma. Hum Pathol 31:185–192

    Article  PubMed  CAS  Google Scholar 

  68. Saito T, Oda Y et al (2000) Prognostic value of the preserved expression of the E-cadherin and catenin families of adhesion molecules and of beta-catenin mutations in synovial sarcoma. J Pathol 192:342–345

    Article  PubMed  CAS  Google Scholar 

  69. Antonescu CR, Tschernyaavsky SJ et al (2001) Prognostic impact of p53 status, TLS-CHOP fusion transcript structure, and histological grade in myxoid liposarcoma: a molecular and clinicopathologic study of 82 cases. Clin Cancer Res 7:3977–3987

    PubMed  CAS  Google Scholar 

  70. Wiechen K, Sers C, Agoulnik A, Arlt K, Dietel M, Schlag PM, Scheider U (2001) Down-regulation of caveolin-1, a candidate tumor suppressor gene, in sarcomas. Am J Pathol 158:833–839

    Article  PubMed  CAS  Google Scholar 

  71. Tomoda R, Seto M, Tsumuki H et al (2002) Telomerase activity and human telomerase reverse transcriptase mRNA expression are correlated with clinical aggressiveness in soft tissue tumors. Cancer 95(5):1127–1133

    Article  PubMed  CAS  Google Scholar 

  72. Kawaguchi K, Oda Y et al (2003) Mechanisms of inactivation of the p16 gene in leyomiosarcoma of soft tissue: the absence of p16 expression correlates with the methylation status and poor prognosis. J Pathol 201:487–495

    Article  PubMed  CAS  Google Scholar 

  73. Oda Y, Takahira T et al (2003) Alterations of cell cycle regulators in mixofibrosarcoma with special emphasis on their prognostic implications. Human Pathol 34:1035–1042

    Article  CAS  Google Scholar 

  74. Oda Y, Ohishi Y et al (2003) Nuclear expression of Y-box-binding protein-1 correlates with P-glycoprotein and topoisomerase II alpha expression, and with poor prognosis in synovial sarcoma. J Pathol 199:251–258

    Article  PubMed  CAS  Google Scholar 

  75. Kawaguchi K, Oda Y et al (2004) Death-associated protein kinase (DAP kinase) alteration in soft tissue leiomyosarcoma: promoter methylation or homozygous deletion is associated with a loss of DAP kinase expression. Hum Pathol 35:1266–1271

    Article  PubMed  CAS  Google Scholar 

  76. Sato O, Wada T et al (2005) Expression of epidermal growth factor receptor, ERB2 and KIT in adult soft tissue sarcoma: a clinicopathologic study of 281 cases. Cancer 103:1881–1890

    Article  PubMed  CAS  Google Scholar 

  77. Oda Y, Yamamoto H et al (2005) Frequent alteration of p16INK4a/p14ARF and p53 pathways of round cell appearance in myxoid/round cell liposarcoma: altered p53 gene and reduced p14ARF expression correlates with poor prognosis. J Pathol 207:410–421

    Article  PubMed  CAS  Google Scholar 

  78. Seidel C, Bartel F et al (2005) Alterations OD cancer-ralted genes in soft tissue sarcomas: hypermethylation of RASSF1A is frequently detected in leiomyosarcoma and associated with poor prognosis in sarcoma. Int J Cancer 114:442–447

    Article  PubMed  CAS  Google Scholar 

  79. Kobayashi C, Oda Y et al (2006) Aberrant expression of CHFR in malignant peripheral nerve sheat tumors. Mod Pathol 19:524–532

    Article  PubMed  CAS  Google Scholar 

  80. Izumi T, Oda Y et al (2006) Prognostic significance od dysadherin expression in epithelioid sarcoma and its diagnostic utility in distinguishing epithelioid sarcoma from rhabdoid tumor. Mod Pathol 19:820–831

    PubMed  CAS  Google Scholar 

  81. Izumi T, Oda Y, Hasegawa T et al (2007) Dysadherin expression as a significant prognosis factor and as a determinant of histologic features in synovial sarcoma: special reference to its inverse relationship with E-cadherin expression. Am J Sur Pathol 31:85–94

    Article  Google Scholar 

  82. Maeda T, Hashitani S, Zushi Y, Segawa E, Tanaka N, Sakurai K, Urade M (2008) Establishment of a nude mouse transplantable model of a human malignant fibrous histiocytoma of the mandible with high metastatic potential to the lung. J Cancer Res Clin Oncol 134(9):1005–1011

    Article  PubMed  Google Scholar 

  83. Oda Y, Tateishi N, Matono H, Matsuura S, Yamamaoto H, Tamiya S, Yokoyama R, Matsuda S, Iwamoto Y, Tsuneyoshi M (2009) Chemokine receptor CXCR4 expression is correlated with VEGF expression and poor survival in soft-tissue sarcoma. Int J Cancer 124(8):1852–1859

    Article  PubMed  CAS  Google Scholar 

  84. Italiano A, Bianchini L, Gjernes E, Keslair F, Ranchere-Vince D, Dumollard JM, Haudebourg J, Leroux A, Mainguené C, Terrier P, Chibon F, Coindre JM, Pedeutour F (2009) Clinical and biological significance of CDK4 amplification in well-differentiated and dedifferentiated liposarcomas. Clin Cancer Res 15(18):5696–5703

    Article  PubMed  CAS  Google Scholar 

  85. Tsiatis AC, Herceg ME, Keedy VL, Halpern JL, Holt GE, Schwartz HS, Cates JM (2009) Prognostic significance of c-Myc expression in soft tissue leiomyosarcoma. Mod Pathol 22(11):1432–1438

    Article  PubMed  CAS  Google Scholar 

  86. Dreux N, Marty M et al (2010) Value and limitation of immunohistochemical expression of HMGA2in mesenchymal tumors: about a series of 1052 cases. Mod Pathol 23(12):1657–1666

    Article  PubMed  CAS  Google Scholar 

  87. Shim BY, Yoo J, Lee YS, Hong YS, Kim HK, Kang JH (2010) Prognostic role of Rb, p16, cyclin D1 proteins in soft tissue sarcomas. Cancer Res Treat 42(3):144–150

    Article  PubMed  Google Scholar 

  88. Lahat G, Tuvin D, Wei C, Wang WL, Pollock RE, Anaya DA, Bekele BN, Corely L, Lazar AJ, Pisters PW, Lev D (2010) Molecular prognosticators of complex karyotype soft tissue sarcoma outcome: a tissue microarray-based study. Ann Oncol 21(5):1112–1120

    Article  PubMed  CAS  Google Scholar 

  89. Lahat G, Zhang P, Zhu QS, Torres K, Ghadimi M, Smith KD, Wang WL, Lazar AJ, Lev D (2011) The expression of c-Met pathway components in unclassified pleomorphic sarcoma/malignant fibrous histiocytoma (UPS/MFH): a tissue microarray study. Histopathology 59(3):556–561

    Article  PubMed  Google Scholar 

  90. Torres KE, Liu J et al (2011) Activated MET is a prognosticator and potential therapeutic target for malignant peripheral nerve sheath tumor. Clin Cancer Res 17(12):3943–3955

    Article  PubMed  CAS  Google Scholar 

  91. Furu M, Kajita Y, Nagayama S, Ishibe T, Shima Y, Nishijo K, Uejima D, Takahashi R, Aoyama T, Nakayama T, Nakamura T, Nakashima Y, Ikegawa M, Imoto S, Katagiri T, Nakamura Y, Toguchida J (2011) Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas. Oncogene 30(38):4015–4025

    Article  PubMed  CAS  Google Scholar 

  92. Carneiro A, Bendahl PO, Åkerman M, Domanski HA, Rydholm A, Engellau J, Nilbert M (2011) Ezrin expression predicts local recurrence and development of metastases in soft tissue sarcomas. J Clin Pathol 64(8):689–694

    Article  PubMed  Google Scholar 

  93. Gasparini P, Facchinetti F et al (2011) Prognostic determinants in epithelioid sarcoma. Eur J Cancer 47(2):287–295

    Article  PubMed  CAS  Google Scholar 

  94. Perissinotto E, Cavalloni G, Leone F, Fonsato V, Mitola S, Grignani G, Surrenti N, Sangiolo D, Bussolino F, Piacibello W, Aglietta M (2005) Involvement of chemokine receptor 4/stromal cell-derived factor 1 system during osteosarcoma tumor progression. Clin Cancer Res 11(2 Pt 1):490–497

    PubMed  CAS  Google Scholar 

  95. Kim SY, Lee CH, Midura BV, Yeung C, Mendoza A, Hong SH, Ren L, Wong D, Korz W, Merzouk A, Salari H, Zhang H, Hwang ST, Khanna C, Helman LJ (2008) Inhibition of the CXCR4/CXCL12 chemokine pathway reduces the development of murine pulmonary metastases. Clin Exp Metastasis 25(3):201–211

    Article  PubMed  CAS  Google Scholar 

  96. Strahm B, Durbin AD, Sexsmith E, Malkin D (2008) The CXCR4-SDF1 alpha axis is a critical mediator of rhabdomyosarcoma metastatic signaling induced by bone marrow stroma. Clin Exp Metastasis 25(1):1–10

    Article  PubMed  CAS  Google Scholar 

  97. Guillou L, Coindre JM, Bonichon F, Nguyen BB, Terrier P, Collin F, Vilain MO, Mandard AM, Le Doussal V, Leroux A et al (1997) Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma. J Clin Oncol 15:350–362

    PubMed  CAS  Google Scholar 

  98. Skubitz KM, Pambuccian S, Manivel JC, Skubitz AP (2008) Identification of heterogeneity among soft tissue sarcomas by gene expression profiles from different tumors. J Transl Med 6(6):23

    Article  PubMed  Google Scholar 

  99. Suehara Y (2011) Proteomic analysis of soft tissue sarcoma. Int J Clin Oncol. 16(2):92–100

    Article  PubMed  CAS  Google Scholar 

  100. Lofti R, Eisenbacher J, Solgi G, Fuchs K, Yildiz T, Nienhaus C, Rojewski MT, Schrezenmeier H (2011) Human mesenchymal stem cells (MSCs) respond to native but not oxidized damage associated molecular pattern molecules (DAMPs) from necrotic (tumor) material. Eur J Immunol 41:2021–2028

    Article  Google Scholar 

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Authors and Affiliations

  1. Division of Melanoma and Sarcoma, European Institute of Oncology, Milan, Italy

    Elisabetta Pennacchioli, Giulio Tosti, Francesco Verrecchia, Claudia Menicanti & Alessandro Testori

  2. Division of Pathology, European Institute of Oncology, Milan, Italy

    Massimo Barberis

  3. Division of Clinical Pharmacology and New Drugs, European Institute of Oncology, Milan, Italy

    Tommaso M. De Pas

  4. Molecular Medicine Program, European Institute of Oncology, Milan, Italy

    Giovanni Mazzarol

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  1. Elisabetta Pennacchioli
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Pennacchioli, E., Tosti, G., Barberis, M. et al. Sarcoma spreads primarily through the vascular system: are there biomarkers associated with vascular spread?. Clin Exp Metastasis 29, 757–773 (2012). https://doi.org/10.1007/s10585-012-9502-4

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  • DOI: https://doi.org/10.1007/s10585-012-9502-4

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