title: Prognostic significance of intratumoral lymphangiogenesis in squamous cell carcinoma of the oral cavity.
abstract: BACKGROUND
  Clinicopathologic data demonstrated that the lymphatic system is the main route for solid tumor metastasis. However, the effect of intratumoral lymphangiogenesis (IL) on prognosis in oral carcinoma is still unknown because, until recently, no reliable markers for lymphatic endothelium were available. The current study analyzed the lymphatic vessels in tumor tissue specimens of patients with primary oral carcinoma using the new marker, PA2.26.
  
  
  METHODS
  The authors investigated IL in surgical tissue samples of 61 patients with early-stage (Stages I-II) oral carcinoma. The tissue specimens were stained for PA2.26 and the correlation between IL and relevant parameters was analyzed by the Pearson chi-square test. In a univariate analysis using the Kaplan-Meier method, IL was analyzed against survival and disease-free period. Statistical significance of differences between distributions was studied by the log-rank test. Clinicopathologic parameters, including IL, were entered in a multivariate analysis to determine independent prognostic significance.
  
  
  RESULTS
  Thirty-three patients had IL. In the follow-up, a strong association was found between IL and locoregional recurrence (30.3 % of the patients with IL and 7.1% of the patients without IL). The presence of IL did not correlate significantly with the pT classification, primary location, or tumor differentiation. IL was found to have no influence on overall survival in univariate analysis, but there was significant association between IL and disease-free survival (P=0.03). Multivariate analysis revealed IL to be the sole independent factor influencing disease-free interval (P=0.02).
  
  
  CONCLUSIONS
  These results suggested that IL is associated with locoregional disease recurrence in early-stage oral carcinoma. The presence of IL was a useful discriminator in predicting the outcome of patients with absence of lymph node metastasis.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Mario Fernando
authors.initials: MF
authors.lastname: Muñoz-Guerra
authors.forename: Eva G
authors.initials: EG
authors.lastname: Marazuela
authors.forename: Esther
authors.initials: E
authors.lastname: Martín-Villar
authors.forename: Miguel
authors.initials: M
authors.lastname: Quintanilla
authors.forename: Carlos
authors.initials: C
authors.lastname: Gamallo
mesh_terms: D001707:Biopsy, Needle; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D046508:Culture Techniques; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D042583:Lymphangiogenesis / Q000502:physiology*; D008297:Male; D009062:Mouth Neoplasms / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis