| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 150, 1951-1957, Copyright © 1997 by American Society for Investigative Pathology
REGULAR ARTICLES |
RM de Waal, MC van Altena, H Erhard, UH Weidle, PT Nooijen and DJ Ruiter
Department of Pathology, University Hospital, Nijmegen, The Netherlands.
Cutaneous melanoma has an initial preference for lymphatic spread. Remarkably, melanoma progression toward this metastasizing phenotype is accompanied by intense blood vessel angiogenesis (hemangiogenesis), but lymphangiogenesis, the formation of new lymph vessels in the tumor, has never been reported. To investigate how primary melanoma cells interact with the existing lymphatic microvasculature, and whether lymphangiogenesis occurs, an immunostaining was developed that differentially decorates blood and lymph vessels in frozen tissue sections. The density and distribution of both these vessel types in and around thin (< or = 1.5 mm) and thick (> or = 1.5 mm) primary melanoma lesions and in normal and uninvolved skin were determined. Although especially in thick melanoma lesions a significant increase in blood vessel density was observed, lymphatic density remained unaltered, showing that lymphangiogenesis did not occur. Morphological analysis indicated, however, that melanoma progression is accompanied by a sequence of events that involves hemangiogenesis supporting tumor expansion, especially in the vertical growth phase. Often, stromal sepia are formed around the blood capillaries in the tumor neovasculature protecting them from invasion. Lymph vessels inside the tumor were infrequently observed. However, subepidermal lymph vessels often seemed to be entrapped and penetrated by the expanding tumor mass. In this way, hemangiogenesis, as the driving force behind tumor expansion, might indirectly increase the chance of lymphatic invasion in the absence of lymphangiogenesis. This model explains the paradox that, although melanoma metastasis seems to require angiogenesis, a consistent relation of prognosis with blood capillary density in primary cutaneous melanoma is lacking.
This article has been cited by other articles:
 |
|
 |
|
  F. Niakosari, H. J. Kahn, D. McCready, D. Ghazarian, L. E. Rotstein, A. Marks, A. Kiss, and L. From Lymphatic Invasion Identified by Monoclonal Antibody D2-40, Younger Age, and Ulceration: Predictors of Sentinel Lymph Node Involvement in Primary Cutaneous Melanoma Arch Dermatol, April 1, 2008; 144(4): 462 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. Posther, M. A. Selim, P. J. Mosca, W. E. Stanley, J. L. Johnson, D. S. Tyler, and H. F Seigler Histopathologic Characteristics, Recurrence Patterns, and Survival of 129 Patients With Desmoplastic Melanoma Ann. Surg. Oncol., May 1, 2006; 13(5): 728 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D Massi, S Puig, A Franchi, J Malvehy, S Vidal-Sicart, M Gonzalez-Cao, G Baroni, S Ketabchi, J Palou, and M Santucci Tumour lymphangiogenesis is a possible predictor of sentinel lymph node status in cutaneous melanoma: a case-control study J. Clin. Pathol., February 1, 2006; 59(2): 166 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Niakosari, H. J. Kahn, A. Marks, and L. From Detection of Lymphatic Invasion in Primary Melanoma With Monoclonal Antibody D2-40: A New Selective Immunohistochemical Marker of Lymphatic Endothelium Arch Dermatol, April 1, 2005; 141(4): 440 - 444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Zhang, C. R. Dass, E. Sumithran, N. Di Girolamo, L.-Q. Sun, and L. M. Khachigian Effect of Deoxyribozymes Targeting c-Jun on Solid Tumor Growth and Angiogenesis in Rodents J Natl Cancer Inst, May 5, 2004; 96(9): 683 - 696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. P. Padera, Y. Boucher, R. K. Jain, L. M. Wein, P. E. Holden, and D. H. Kirn Correspondence re: S. Maula et al., Intratumoral Lymphatics Are Essential for the Metastatic Spread and Prognosis in Squamous Cell Carcinoma of the Head and Neck. Cancer Res., 63: 1920-1926, 2003. Cancer Res., December 1, 2003; 63(23): 8555 - 8557. [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Dadras, T. Paul, J. Bertoncini, L. F. Brown, A. Muzikansky, D. G. Jackson, U. Ellwanger, C. Garbe, M. C. Mihm, and M. Detmar Tumor Lymphangiogenesis: A Novel Prognostic Indicator for Cutaneous Melanoma Metastasis and Survival Am. J. Pathol., June 1, 2003; 162(6): 1951 - 1960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Straume, D. G. Jackson, and L. A. Akslen Independent Prognostic Impact of Lymphatic Vessel Density and Presence of Low-Grade Lymphangiogenesis in Cutaneous Melanoma Clin. Cancer Res., January 1, 2003; 9(1): 250 - 256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Clarijs, L. Schalkwijk, U. B. Hofmann, D. J. Ruiter, and R. M. W. de Waal Induction of Vascular Endothelial Growth Factor Receptor-3 Expression on Tumor Microvasculature as a New Progression Marker in Human Cutaneous Melanoma Cancer Res., December 1, 2002; 62(23): 7059 - 7065. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-J. Lee, N. Nagai, C.-H. Siar, K. Nakano, H. Nagatsuka, H. Tsujigiwa, C.-H. Roan, and M. Gunduz Angioarchitecture of Primary Oral Malignant Melanomas J. Histochem. Cytochem., November 1, 2002; 50(11): 1555 - 1562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Jain and T. P. Padera Prevention and Treatment of Lymphatic Metastasis by Antilymphangiogenic Therapy J Natl Cancer Inst, June 5, 2002; 94(11): 785 - 787. [Full Text] [PDF]
|
|
|
|
|
|
Y. He, K.-i. Kozaki, T. Karpanen, K. Koshikawa, S. Yla-Herttuala, T. Takahashi, and K. Alitalo Suppression of Tumor Lymphangiogenesis and Lymph Node Metastasis by Blocking Vascular Endothelial Growth Factor Receptor 3 Signaling J Natl Cancer Inst, June 5, 2002; 94(11): 819 - 825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Oliver and M. Detmar The rediscovery of the lymphatic system: old and new insights into the development and biological function of the lymphatic vasculature Genes & Dev., April 1, 2002; 16(7): 773 - 783. [Full Text] [PDF]
|
|
|
|
|
|
R. K. Jain and B. T. Fenton Intratumoral Lymphatic Vessels: A Case of Mistaken Identity or Malfunction? J Natl Cancer Inst, March 20, 2002; 94(6): 417 - 421. [Full Text] [PDF]
|
|
|
|
|
|
J. D. White, P. W. Hewett, D. Kosuge, T. McCulloch, B. C. Enholm, J. Carmichael, and J. C. Murray Vascular Endothelial Growth Factor-D Expression Is an Independent Prognostic Marker for Survival in Colorectal Carcinoma Cancer Res., March 1, 2002; 62(6): 1669 - 1675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Karpanen and K. Alitalo Lymphatic Vessels as Targets of Tumor Therapy? J. Exp. Med., September 17, 2001; 194(6): F37 - F42. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Clarijs, L. Schalkwijk, D. J. Ruiter, and R. M. W. de Waal Lack of Lymphangiogenesis Despite Coexpression of VEGF-C and Its Receptor Flt-4 in Uveal Melanoma Invest. Ophthalmol. Vis. Sci., June 1, 2001; 42(7): 1422 - 1428. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. D. Nathanson, R. J. Zarbo, D. L. Wachna, C. A. Spence, T. A. Andrzejewski, and J. Abrams Microvessels That Predict Axillary Lymph Node Metastases in Patients With Breast Cancer Arch Surg, May 1, 2000; 135(5): 586 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Valtola, P. Salven, P. Heikkila, J. Taipale, H. Joensuu, M. Rehn, T. Pihlajaniemi, H. Weich, R. deWaal, and K. Alitalo VEGFR-3 and Its Ligand VEGF-C Are Associated with Angiogenesis in Breast Cancer Am. J. Pathol., May 1, 1999; 154(5): 1381 - 1390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lymboussaki, T. A. Partanen, B. Olofsson, J. Thomas-Crusells, C. D. M. Fletcher, R. M. W. de Waal, A. Kaipainen, and K. Alitalo Expression of the Vascular Endothelial Growth Factor C Receptor VEGFR-3 in Lymphatic Endothelium of the Skin and in Vascular Tumors Am. J. Pathol., August 1, 1998; 153(2): 395 - 403. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
