title: Prognostic significance of lymphangiogenesis in pharyngolaryngeal carcinoma patients.
abstract: BACKGROUND
  Lymphatic vessel spread is considered a major route for head and neck squamous cell carcinoma metastasis. Formation of new lymphatic vessels could facilitate the process, raising the malignant potential of these tumours. Recent identification of lymphatic markers allows the study of the lymphangiogenesis phenomenon. We searched for molecular events involved in the lymphangiogenic process that could have prognostic value in laryngeal/pharyngeal carcinoma patients.
  
  
  METHODS
  104 paraffin-embedded pharyngeal/laryngeal tumour samples were studied. Immunohistochemical analysis of podoplanin and double immunofluorescence analysis of Ki-67 and D2-40 were performed. Lymph vessel density (inside the tumour mass, at its periphery or considered as a whole) and the presence of tumour emboli inside lymphatics were recorded. The proliferative state of endothelial lymphatic cells was evaluated.
  
  
  RESULTS
  Lymphatic vessels were detected inside the tumour mass (75%) and in the surrounding tissue (80%); some of them in a proliferative state. Tumour emboli were detected in a high proportion of the cases (45%). Lymphatic vessel density was higher in the pharyngeal cases (p = 0.0029), in greater size (p = 0.039), more advanced stage primary tumours (p = 0.006) and in carcinomas of patients with affected nodes (p = 0.019). The presence of tumour emboli and a high global vessel density were indicators of poor prognosis (recorded as death from tumour) in the laryngeal group (p = 0.015 and p = 0.027, respectively), but notably not in the pharyngeal one. Interestingly, high global vessel density showed a negative prognostic value among pathologically staged N0 laryngeal carcinomas (p = 0.03).
  
  
  CONCLUSIONS
  The lymphangiogenic process correlated with aggressive tumour features (pN category, tumour size, tumour stage), but might play different roles in tumours arising from different anatomic sites. Our results suggest that detection of tumour emboli and assessment of global vessel density using the D2-40 antibody, may be useful in the clinical practice, as predictors of reduced survival among pN0 laryngeal carcinoma patients.
authors.affiliation: Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Asturias, Spain.
authors.forename: Darío
authors.initials: D
authors.lastname: Garcia-Carracedo
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Rodrigo
authors.forename: Aurora
authors.initials: A
authors.lastname: Astudillo
authors.forename: Carlos Suarez
authors.initials: CS
authors.lastname: Nieto
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Gonzalez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000556:secondary; D049109:Cell Proliferation; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010610:Pharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; C500987:monoclonal antibody D2-40