title: Tumor lymphangiogenesis predicts melanoma metastasis to sentinel lymph nodes.
abstract: Cutaneous melanoma is a common melanocytic neoplasm that can quickly metastasize to regional lymph nodes. Currently, prognosis is determined by measuring tumor thickness but more reliable markers for metastatic spread are urgently needed. We investigated whether the extent of tumor lymphangiogenesis can predict melanoma metastasis to sentinel lymph nodes. We quantified the extent of tumor lymphangiogenesis, as well as other factors, in excised primary tumors and in sentinel lymph node biopsy samples from 45 patients with primary cutaneous melanoma. The results were correlated with histological and clinical outcome. Primary melanomas from patients whose tumors had metastasized to the sentinel lymph nodes contained prominent 'hot spots' of increased lymphatic vessel density, compared to nonmetastatic tumors. Multivariate risk analysis revealed that the lymphatic vascular area of primary melanomas, an index of tumor lymphangiogenesis, was the most sensitive prognostic marker for sentinel lymph node metastasis, and was even able to more accurately predict which tumors were metastatic to sentinel lymph nodes than the currently used method of measuring tumor thickness. Highly lymphangiogenic melanomas maintained their lymphangiogenic activity after metastasis to the sentinel lymph node. The extent of tumor lymphangiogenesis is a highly sensitive (83%) and specific (89%) prognostic marker of lymph node metastasis. Assessment of lymphangiogenesis in primary melanomas may be a more effective approach than the currently used technique of measuring tumor thickness in selecting patients with early metastatic disease for aggressive therapy.
authors.affiliation: Cutaneous Biology Research Center and Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. sdadras@partners.org
authors.forename: Soheil S
authors.initials: SS
authors.lastname: Dadras
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lange-Asschenfeldt
authors.forename: Paula
authors.initials: P
authors.lastname: Velasco
authors.forename: Lynh
authors.initials: L
authors.lastname: Nguyen
authors.forename: Anish
authors.initials: A
authors.lastname: Vora
authors.forename: Alona
authors.initials: A
authors.lastname: Muzikansky
authors.forename: Katharina
authors.initials: K
authors.lastname: Jahnke
authors.forename: Axel
authors.initials: A
authors.lastname: Hauschild
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirakawa
authors.forename: Martin C
authors.initials: MC
authors.lastname: Mihm
authors.forename: Michael
authors.initials: M
authors.lastname: Detmar
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D042583:Lymphangiogenesis / Q000502:physiology*; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D011379:Prognosis; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis; D042643:Vascular Endothelial Growth Factor D / Q000096:biosynthesis; D033921:Vesicular Transport Proteins
chemical_list: D014408:Biomarkers, Tumor; D006023:Glycoproteins; C119248:LYVE1 protein, human; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D033921:Vesicular Transport Proteins