title: Lymphatic invasion is independently prognostic of metastasis in primary cutaneous melanoma.
abstract: OBJECTIVE
  Lymphatic invasion (LI) in primary cutaneous melanomas was recently found to be common. In this study, we evaluated LI as an independent prognostic factor.
  
  
  METHODS
  This study included 251 patients with vertical growth phase (VGP) primary cutaneous melanomas who had paraffin-fixed lesional tissue and were in a prospective cohort seen between 1972 and 1991, had no clinical evidence of regional nodal disease at diagnosis, and had at least ten years of follow-up. Dual immunohistochemical staining was used to detect lymphatic endothelium (podoplanin) and melanoma cells (S-100). Multivariate logistic regression for ten-year metastasis was used to define independent prognostic factors, and a prognostic tree was developed to characterize and discriminate risk groups. Kaplan-Meier disease-free survival curves for those with and without LI within current American Joint Committee on Cancer stages were compared using the log-rank statistic.
  
  
  RESULTS
  LI was observed in 43% (108 of 251) of the study melanomas. The multivariate model for ten-year metastasis identified four independent prognostic factors: tumor thickness, mitotic rate, LI, and anatomic site. The prognostic tree identified a group of patients with thin (≤1 mm thick) melanomas and poor prognosis: stage IB melanomas with LI. Survival curves for time to first metastasis showed significantly poorer prognosis for patients with LI compared with those without it for both stages IB and IIA.
  
  
  CONCLUSIONS
  LI is common across the range of tumor thicknesses in primary VGP melanomas. It is an independent prognostic factor and significantly increases the risk of metastasis in patients in clinical stages IB and IIA.
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xu
authors.forename: Lianjun
authors.initials: L
authors.lastname: Chen
authors.forename: DuPont
authors.initials: D
authors.lastname: Guerry
authors.forename: Peter R
authors.initials: PR
authors.lastname: Dawson
authors.forename: Wei-ting
authors.initials: WT
authors.lastname: Hwang
authors.forename: Patricia
authors.initials: P
authors.lastname: VanBelle
authors.forename: David E
authors.initials: DE
authors.lastname: Elder
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Zhang
authors.forename: Michael E
authors.initials: ME
authors.lastname: Ming
authors.forename: Lynn
authors.initials: L
authors.lastname: Schuchter
authors.forename: Phyllis A
authors.initials: PA
authors.lastname: Gimotty
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000378:metabolism / Q000556:secondary*; D015996:Survival Rate; D000098853:Podoplanin
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin
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