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Clinical & Experimental Metastasis
Published in: Clinical & Experimental Metastasis 6/2007

01-10-2007 | Research Paper

Immunoexpression of endoglin in brain metastasis secondary to malignant melanoma: evaluation of angiogenesis and comparison with brain metastasis secondary to breast and lung carcinomas

Authors: Karina B. Salgado, Nadima V. Toscani, Leonardo L. M. Silva, Arlete Hilbig, Ligia Maria Barbosa-Coutinho

Published in: Clinical & Experimental Metastasis | Issue 6/2007

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Abstract

Brain metastases are linked to poor prognosis. After carcinomas of the lung and breast, malignant melanomas (MM) are the next type of neoplasm with the higher metastatic dissemination involving the central nervous system and that has the worst prognosis after metastasis has been diagnosed. Angiogenesis has been linked to tumor growth and metastasis. Among the immunomarkers of angiogenesis, endoglin (CD105) is the most specific antibody, since it is a marker for tumor endothelium, and expression of CD105 has been observed to be associated with prognosis in several types of tumor, which is not always observed in melanomas. This study investigated angiogenesis in brain metastasis secondary to malignant melanomas and compared these with brain metastasis secondary to carcinomas of the lung and breast, through expression of CD105 (endoglin). The study investigated 93 cases of brain metastasis secondary to MM (33) and carcinomas of the lung (31) and breast (29), assessing endoglin immunoexpression, number of microvessels and diameter of tumor vessels. Tumor microvessels were counted using a modified version of the Chalkley technique. The observed difference between MM and breast carcinoma was statistically significant (P = 0.026). The difference between MM and lung carcinoma was not significant (P = 0.218). Vascular diameter observation revealed no statistical difference between the vascular size of neoplastic vessels in MM and in breast and lung carcinomas. Of the tumors investigated here, malignant melanomas were shown to have the lowest number of microvessels and had intermediate tumor vessel diameter as compared to carcinomas of the lungs and breast. Such results were not expected to be found in neoplasms such as melanomas that, besides presenting high dissemination capacity, have a high index of hemorrhage secondary to brain metastasis.
Literature
1.
O’Neil BP, Buckner JC, Coffey RJ, Dinapoli RP, Shaw EG (1994) Brain metastatic lesions. Mayo Clin Proc 69:1062–1068
2.
Bafaloukos D, Gogas H (2004) The treatment of brain metastasis in melanoma patients. Cancer Treat Rev 30:515–520PubMedCrossRef
3.
Tosoni A, Ermani M, Brandes AA (2004) The pathogenesis and treatment of brain metastasis: a comprehensive review. Crit Rev Oncol Hematol 52:199–215PubMedCrossRef
4.
5.
Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis: correlation in invasive breast carcinoma. N Engl J Med 324:1–8PubMedCrossRef
6.
Kumar S, Ghellal A, Li C, Byrne G, Haboubi N, Wang JM, Bundred N (1999) Breast carcinoma: vascular density determined using CD 105 antibody correlates with tumor prognosis. Cancer Res 59:856–861PubMed
7.
Duff SE, Li C, Garland JM, Kumar S (2003) CD 105 is important for angiogenesis: evidence and potencial applications. The Faseb Journal 17(9):984–992PubMedCrossRef
8.
9.
Yano S, Shinohara H, Herbst RS, Kuniyasu H, Bucana CD, Ellis LM, Davis DW, McConkey DJ, Fiedler IJ (2000) Expression of vascular growth factor is necessary but not sufficient for production and growth of brain metastasis. Cancer Res 60:4959–67PubMed
10.
Nicolson GL, Menter DG, Herrmann JL, Yun Z, Cavanaugh P, Marchetti D (1996) Brain metastasis: role of trophic, autocrine, and paracrine factors in tumor invasion and colonization of the central nervous system. Curr Top Microbiol Immunol 213(Pt 2):89–115PubMed
11.
Kashani-Sabet M, Sagebiel RW, Ferreira CMM, Nosrati M, Miller JR III (2002) Tumor vascularity in the prognostic assessment of primary cutaneous melanoma. J Clin Oncol 20(7):1826–1831PubMedCrossRef
12.
Srivastava A, Laidler P, Davies RP, Horgan K, Hughes LE (1988) The prognostic significance of tumor vascularity in intermediate thickness (0.76–4.0 mm thick) skin melanoma: a quantitative histologic study. Am J Pathol 133:419–423PubMed
13.
Followfield ME, Cook MG (1991) The vascularity of primary cutaneous melanoma. J Pathol 164:241–244CrossRef
14.
Barnhill RL, Fandrey K, Levy MA, Mihm MC Jr, Hyman B (1992) Angiogenesis and tumor progression of melanoma: quantification of vascularity in melanocytic nevi and cutaneous malignant melanoma. Lab Invest 67(3):331–337PubMed
15.
Busam KJ, Berwick M, Blessing K, Fandrey K, Kang S, Karaoli T, Fine J, Cochran AJ, White WL, Rivers J (1995) Tumor vascularity is not a prognostic factor for skin melanoma. Am J Pathol 147:1049–1056PubMed
16.
Maniotis A, Folberg R, Hess A, Seftor EA, Gardner LMG, Pe’er J, Trent JM, Meltzer PS, Hendrix MJC (1999) Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 155:739–752PubMed
17.
Wilkstrom P, Lissbrandt I, Stattin P, Egevad L, Bergh A (2002) Endoglin (CD105) is expressed on immature blood vessels and is a marker for survival in prostate cancer. Prostate 51(4):268–275CrossRef
18.
Martone T, Rosso P, Albera P, Migliaretti G, Fraire F, Pignataro L, Pruneri G, Bellone G, Cortesina G (2005) Prognostic relevance of CD 105+ microvessel density in HNSCC patient outcome. Oral Oncol 41:147–155PubMedCrossRef
19.
Offersen BV, Borre M, Sorensen FB, Overgaard J (2002) Comparison of methods of microvascular staining and quantification in prostate carcinoma: relevance to prognosis. APMIS 110:177–185PubMedCrossRef
20.
Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364PubMedCrossRef
21.
Offersen BV, Borre M, Overgaard J (2003) Quantification of angiogenesis as a prognostic marker in human carcinomas: a critical evaluation of histopathological methods for estimation of vascular density. Eur Jour Can 39:881–890 CrossRef
22.
Sharma S, Sharma MC, Sarkar C (2005) Morphology of angiogenesis in human cancer: a conceptual overview, histoprognostic perspective and significance of neoangiogenesis. Histopathology 46:481–489PubMedCrossRef
23.
Folkman J (1995) Clinical applications of research on angiogenesis. N Engl J Med 333(26):1757–1763 PubMedCrossRef
24.
Miller KD, Sweeney CJ, Sledge GW Jr (2001) Redefining the target: chemotherapeutics as antiangiogenics. J Clin Oncol 19(4):1195–1206PubMed
25.
Scappaticci FA (2002) Mechanisms and future directions for angiogenesis-based cancer therapies. J Clin Oncol 18:3906–3927CrossRef
26.
27.
Kerbel R, Folkman J (2002) Clinical translation of angiogenesis inhibitors. Nat Ver Cancer 2(10):727–739CrossRef
28.
Jain RK (2001) Normalizing tumor vasculature with antiangiogenic therapy: a new paradigm for combination therapy. Nat Med 7(9):987–989PubMedCrossRef
29.
Clouston PD, De Angelis LM, Posner JB (1992) The spectrum of neurological disease in patients with systemic cancer. Ann Neurol 31:268–273PubMedCrossRef
30.
Py W, Loeffler JS (1999) Management of brain metastasis. Oncology 13:941–961
31.
Posner JB (1977) Management of central nervous system metastasis. Semin Oncol 4:81–91PubMed
32.
Fiedler I, Yano S, Zhang R (2002) The seed and soil hypothesis: vascularisation and brain metastasis. Lancet Oncol 3:53–57 CrossRef
33.
Brewer CA, Setterdahl JJ, Li MJ, Johnston JM, Mann JL, Mcasey ME (2000) Endoglin expression as a measure of microvessel density in cervical cancer. Obstet Gynecol 26:224–228CrossRef
34.
Tanaka F, Otake Y, Yanagihara K, Kawano Y, Miyahara R, Li M, Yamada T, Hanaoka N, Inui K, Wada H (2001) Evaluation of angiogenesis in non-small cell lung cancer: comparison between Anti-CD 34 antibody and Anti-CD 105 antibody. Clin Cancer Res 7:3410–3415PubMed
35.
Fonsatti E, Maio M (2004) Highlights on endoglin (CD 105): from basis findings towards clinical applications in human cancer. Journal of Translational Medicine 2(1):18PubMedCrossRef
36.
Chalkley H (1943) Method for the quantitative morphological analysis of tissues. J Natl Cancer 4:47–53
37.
38.
Depasquale I, Thompson WD (2005) Microvessel density for melanoma prognosis. Histopathology 47:186–194 PubMedCrossRef
39.
Vermeulen PB, Gasparini G, Fox SB, Colpaert C, Marson LP, Gion M, Beliën JAM, de Waal RMW, Van Marck E, Magnani E, Weidner N, Harris AL, Dirix LY (2002) Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumors. Eur Jour Can 38:1564–1579CrossRef
40.
Straume O, Akslen LA (2001) Expression of vascular endothelial growth factor, its receptors(FLT-1, KDR) e TSP-1 related to microvessel density and patient outcome in vertical growth phase melanomas. Am J Pathol 159:223–235PubMed
41.
Rafii S, Heissig B, Hattori K (2002) Efficient mobilization and recruitment of bone-marrow-derived endothelial and hematopoietic stem cells by adenoviral vectors expressing angiogenic factors. Gene Ther 9:631–641PubMedCrossRef
42.
Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Scatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967PubMedCrossRef
43.
Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zagzag D, Yancopoulos GD, Wiegang SJ (1999) Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 284:1994–1998PubMedCrossRef
44.
Chang IS, di Tomaso E, McDonald DM, Jones R, Jain RK, Munn LL (2001) Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proc Natl Acad Sci USA 98(2):398–400CrossRef
45.
Auguste P, Lemiere S, Larrieu-Lahargue F, Bikfalvi A (2005) Molecular mechanisms of tumor vascularization. Crit Rev Oncology/Hematology 54:53–61CrossRef
46.
47.
Shirakawa K, Kobayashi H, Heike Y, Kawamoto S, Brechbiel MW, Kasumi F, Iwanaga T, Konishi F, Terada M, Wakasugi H (2002) Hemodynamics in vasculogenic mimicry and angiogenesis of inflammatory breast cancer xenograft. Cancer Res 62:560–566PubMed
48.
Clarijs R, Otte-Höller I, Riter DJ, de Waal RMW (2002) Presence of a fluid-conducting meshwork in xenografted cutaneous and primary human uveal melanoma. Invest Ophthalm Vis Sci 43(4):912–918
49.
Kellner B (1941) Die fettmorphologie der sarkome. Z Krebsforsch 52:240–246
50.
Inai T, Mancuso M, Hashizume H, Baffert F, Haskell A, Baluk P, Hu-Lowe DD, Shalinsky DR, Thurston G, Yancopoulos GD, McDonald DM (2004) Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Path 165:35–52PubMed
51.
Baluk P, Hashizume H, McDonald D (2005) Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev 15:102–11 PubMedCrossRef
52.
McDonald DM, Baluk P (2005) Imaging of angiogenesis in inflamed airways and tumors: newly formed blood vessels are not alike and may be wildly abnormal: parker B. Francis Lecture. Chest 128(6 Suppl):602S–608S
53.
Hlatky L, Hahnfeldt P, Folkman J (2002) Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn´t tell us. J Natl Cancer Inst 94:883–893PubMed
Metadata
Title
Immunoexpression of endoglin in brain metastasis secondary to malignant melanoma: evaluation of angiogenesis and comparison with brain metastasis secondary to breast and lung carcinomas
Authors
Karina B. Salgado
Nadima V. Toscani
Leonardo L. M. Silva
Arlete Hilbig
Ligia Maria Barbosa-Coutinho
Publication date
01-10-2007
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 6/2007
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-007-9077-7

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