title: Lymphatic spread in squamous cell carcinoma of the penis is independent of elevated lymph vessel density.
abstract: OBJECTIVE
  To examine the potential effect of tumour-induced lymphangiogenesis in squamous cell carcinoma of the penis as a possible mechanism responsible for lymphatic spread.
  
  
  METHODS
  Specimens from 65 patients with invasive tumours (31 with and 34 without metastases) were evaluated for lymphatic vessel density (LVD) by the 'hot-spot' method as the density of lymphatic endothelium hyaluronan receptor (LYVE-1)-positive lymphatic vessels per unit area of tissue. LVD was examined in peritumoral, intratumoral and normal tissue areas. The LVD of each tumour in these locations was calculated as the mean of the three highest lymph vessel counts in three to five hot-spots. The nodal status was based on histopathological examination or an uneventful follow-up of >or=2 years.
  
  
  RESULTS
  In all patients the mean (SD) peritumoral LVD of 8.05 (3.14)/0.75 mm(2) was significantly higher than for intratumoral and normal tissue, of 4.67 (2.58) and 5.20 (1.87), respectively (P < 0.001). The slightly lower intratumoral LVD than in normal tissue was not significant. The peritumoral LVD was 8.07 (3.29) in metastatic and 8.03 (3.03) in non-metastatic carcinomas. The intratumoral LVD was 5.13 (3.01) in node-positive carcinomas and 4.28 (2.15) in tumours with no lymphatic node metastasis (LNM). Comparing tumours with and without LNM, there was no statistically significant difference between intra- and peritumoral LVD.
  
  
  CONCLUSIONS
  Increased LVD does not significantly affect the lymphatic spread in penile carcinomas, indicating that there must be alternative mechanisms that selectively enable tumour cells to invade lymph vessels and to metastasize into the lymph nodes.
authors.affiliation: Department of Urology and Paediatric Urology, University Hospitsl Schleswig Holstein, Campus Kiel, Kiel, Germany. c.naumann@urology.uni-kiel.de
authors.forename: Carsten Maik
authors.initials: CM
authors.lastname: Naumann
authors.forename: Amr
authors.initials: A
authors.lastname: Al-Najar
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Alkatout
authors.forename: Axel
authors.initials: A
authors.lastname: Hegele
authors.forename: Joanna Beate
authors.initials: JB
authors.lastname: Korda
authors.forename: Christian
authors.initials: C
authors.lastname: Bolenz
authors.forename: Holger
authors.initials: H
authors.lastname: Kalthoff
authors.forename: Bence
authors.initials: B
authors.lastname: Sipos
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Juenemann
authors.forename: Christof
authors.initials: C
authors.lastname: van der Horst
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000556:secondary*; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D042583:Lymphangiogenesis / Q000502:physiology*; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010412:Penile Neoplasms / Q000401:mortality / Q000473:pathology*; D016019:Survival Analysis