Prognostic Significance of Tumor-Associated Lymphangiogenesis in Malignant Melanomas of the Conjunctiva

被引:51
作者
Heindl, Ludwig M. [1 ,2 ]
Hofmann-Rummelt, Carmen [1 ,2 ]
Adler, Werner [3 ]
Bosch, Jacobus J. [4 ]
Holbach, Leonard M. [1 ,2 ]
Naumann, Gottfried O. H. [1 ,2 ]
Kruse, Friedrich E. [1 ,2 ]
Cursiefen, Claus [1 ,2 ]
机构
[1] Univ Erlangen Nurnberg, Dept Ophthalmol, D-91054 Erlangen, Germany
[2] Univ Erlangen Nurnberg, Hosp Eye, D-91054 Erlangen, Germany
[3] Univ Erlangen Nurnberg, Dept Med Informat Biometry & Epidemiol, D-91054 Erlangen, Germany
[4] Univ Erlangen Nurnberg, Dept Internal Med Hematol & Oncol 5, D-91054 Erlangen, Germany
关键词
SQUAMOUS-CELL CARCINOMA; CILIARY-BODY-MELANOMAS; EXTRAOCULAR-EXTENSION; METASTASIS; ANGIOGENESIS; LYMPHATICS; NEOVASCULARIZATION; MACROPHAGES; RECURRENCE; PODOPLANIN;
D O I
10.1016/j.ophtha.2011.05.025
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Purpose: To evaluate whether tumor-associated lymphangiogenesis contributes to prognosis of conjunctival malignant melanomas and to study its association with other tumor characteristics. Design: Nonrandomized, retrospective case series. Participants: A total of 109 consecutive patients with primary conjunctival malignant melanoma. Methods: Proliferating lymphatic vessels were identified immunohistochemically using lymphatic vascular endothelial hyaluronan receptor-1 and podoplanin as specific lymphatic endothelial markers and Ki-67 as proliferation marker. Baseline tumor characteristics included tumor location, tumor thickness, tumor diameter, tumor origin, and tumor growth pattern. Kaplan-Meier and Cox regression analyses of the risk of local recurrence, lymphatic spread, distant metastasis, and melanoma-related death were performed. Main Outcome Measures: Intratumoral lymphatic vascular density and its association with tumor characteristics and recurrence-free, lymphatic spread-free, distant metastasis-free, and melanoma-specific survival. Results: Intratumoral and peritumoral proliferating lymphatic vessels could be detected in all of the 109 conjunctival melanoma samples. High intratumoral lymphatic density was significantly associated with palpebral tumor location (P<0.001), greater tumor thickness (P<0.001), larger tumor diameter (P = 0.001), tumor origin de novo (P= 0.002), and nodular tumor growth pattern (P = 0.037). Patients with high intratumoral lymphatic density revealed significantly lower recurrence-free, lymphatic spread-free, distant metastasis-free, and melanoma-specific survival rates (P<0.001 for all). By multivariate Cox regression, factors predictive of local recurrence included palpebral tumor location (hazard ratio [HR] 2.66, P = 0.014), large tumor diameter (HR 5.48, P<0.001), and high intratumoral lymphatic density (HR 2.48, P = 0.043); factors predictive of lymphatic spread included palpebral tumor location (HR 4.13, P = 0.009), high tumor thickness (HR 12.17, P<0.001), and high intratumoral lymphatic density (HR 6.79, P = 0.019); factors predictive of distant metastasis included palpebral tumor location (HR 7.63, P<0.001), high tumor thickness (HR 8.60, P<0.001), large tumor diameter (HR 0.30, P = 0.029), and high intratumoral lymphatic density (HR 8.90, P = 0.047); and factors predictive of melanoma-related death included palpebral tumor location (HR 7.74, P<0.001), high tumor thickness (HR 10.88, P<0.001), large tumor diameter (HR 0.28, P = 0.018), and, with borderline significance, high intratumoral lymphatic density (HR 8.46, P = 0.052). Conclusions: Tumor-associated lymphangiogenesis seems to be associated with an increased risk of local recurrence, lymphatic spread, distant metastasis, and melanoma-related death in patients with conjunctival malignant melanomas. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2011; 118: 2351-2360 (C) 2011 by the American Academy of Ophthalmology.
引用
收藏
页码:2351 / 2360
页数:10
相关论文
共 45 条
[1]   Prognostic value of clinical and histopathological parameters in conjunctival melanomas: a retrospective study [J].
Anastassiou, G ;
Heiligenhaus, A ;
Bechrakis, N ;
Bader, E ;
Bornfeld, N ;
Steuhl, KP .
BRITISH JOURNAL OF OPHTHALMOLOGY, 2002, 86 (02) :163-167
[2]   LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan [J].
Banerji, S ;
Ni, J ;
Wang, SX ;
Clasper, S ;
Su, J ;
Tammi, R ;
Jones, M ;
Jackson, DG .
JOURNAL OF CELL BIOLOGY, 1999, 144 (04) :789-801
[3]  
Beasley NJP, 2002, CANCER RES, V62, P1315
[4]   Blockade of VEGFR3-signalling specifically inhibits lymphangiogenesis in inflammatory corneal neovascularisation [J].
Bock, Felix ;
Onderka, Jasmine ;
Dietrich, Tina ;
Bachmann, Bjoern ;
Pytowski, Bronislaw ;
Cursiefen, Claus .
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 2008, 246 (01) :115-119
[5]   Bevacizumab as a potent inhibitor of inflammatory corneal angiogenesis and lymphangiogenesis [J].
Bock, Felix ;
Onderka, Jasmine ;
Dietrich, Tina ;
Bachmann, Bjorn ;
Kruse, Friedrich E. ;
Paschke, Matthias ;
Zahn, Grit ;
Cursiefen, Claus .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2007, 48 (06) :2545-2552
[6]   Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries -: Podoplanin as a specific marker for lymphatic endothelium [J].
Breiteneder-Geleff, S ;
Soleiman, A ;
Kowalski, H ;
Horvat, R ;
Amann, G ;
Kriehuber, E ;
Diem, K ;
Weninger, W ;
Tschachler, E ;
Alitalo, K ;
Kerjaschki, D .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 154 (02) :385-394
[7]  
Cursiefen C, 2002, INVEST OPHTH VIS SCI, V43, P2127
[8]   VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment [J].
Cursiefen, C ;
Chen, L ;
Borges, LP ;
Jackson, D ;
Cao, JT ;
Radziejewski, C ;
D'Amore, PA ;
Dana, MR ;
Wiegand, SJ ;
Streilein, JW .
JOURNAL OF CLINICAL INVESTIGATION, 2004, 113 (07) :1040-1050
[9]   GS-101 Antisense Oligonucleotide Eye Drops Inhibit Corneal Neovascularization Interim Results of a Randomized Phase II Trial [J].
Cursiefen, Claus ;
Bock, Felix ;
Horn, Folkert K. ;
Kruse, Friedrich E. ;
Seitz, Berthold ;
Borderie, Vincent ;
Frueh, Beatrice ;
Thiel, Michael A. ;
Wilhelm, Frank ;
Geudelin, Bernard ;
Descohand, Isabelle ;
Steuhl, Klaus-Peter ;
Hahn, Angela ;
Meller, Daniel .
OPHTHALMOLOGY, 2009, 116 (09) :1630-1637
[10]   Tumor lymphangiogenesis - A novel prognostic indicator for cutaneous melanoma metastasis and survival [J].
Dadras, SS ;
Paul, T ;
Bertoncini, J ;
Brown, LF ;
Muzikansky, A ;
Jackson, DG ;
Ellwanger, U ;
Garbe, C ;
Mihm, MC ;
Detmar, M .
AMERICAN JOURNAL OF PATHOLOGY, 2003, 162 (06) :1951-1960