Los vasos linfáticos intratumorales y la expresión del VEGF-C son factores predictivos de recidiva ganglionar en el carcinoma epidermoide larningofaríngeo T1-T4 N0

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina. Departamento de Cirugía. Fecha de lectura: 21 de Julio de 200

Polymorphisms in HIF-1alpha affect presence of lymph node metastasis and can influence tumor size in squamous-cell carcinoma of the glottic larynx

et al.[Background]: HIF-1alpha plays a key role in the development and progression of cancer. Its polymorphic variants C1772T and G1790A have been associated with greater susceptibility to cancer and increased tumor progression. [Methods]: We determined the distribution of these polymorphisms among 121 patients with glottic cancer and 154 healthy volunteers by PCR-RFLP. We also analyzed the relationship between the presence of these polymorphisms and various clinicopathologic variables. [Results]: Advanced tumors (T3-T4) were associated with the TT variant (p = 0.036), which was present in 75 % of T4 tumors (p = 0.008). Among patients with nodal metastasis (N+), 41.7 and 22 % were carrying the TT and GA variants, respectively, compared with 9.4 and 2 % of the patients with no metastasis (N0), (p = 0.006 and p = 0.032). [Conclusions]: The presence of the TT and GA variants were associated with lymph node metastasis, while the presence of the TT variant can be associated with larger tumor size.This work was supported by the Foundation for Biomedical Research, Hospital Universitario de La Princesa.Peer Reviewe

Intratumoral lymphatic vessels and VEGF-C expression are predictive factors for lymph node relapse in T1-T4 N0 laryngopharyngeal squamous cell carcinoma

[Background]: The presence of intratumoral lymphatic vessels (ILVs) and the expression of vascular endothelial growth factor-C (VEGF-C) in tumour cells have been studied as markers of lymphangiogenesis in order to evaluate their role in metastatic dissemination in laryngopharyngeal squamous cell carcinoma. [Methods]: A retrospective study was performed in 76 patients of N0 laryngopharyngeal carcinoma. with variable tumour size (T1-T4), histological grade, and location (supraglottic, glottic and hypopharyngeal). The presence of ILVs, as revealed by the expression of PA2.26 antigen and VEGF-C expression, were determined by immunohistochemistry (IHC). Low-grade and high-grade lymphangiogenesis were defined by qualitative and quantitative criteria. [Results]: Multivariate analysis revealed low-grade ILV and VEGF-C expression to be associated respectively with 30.3- and 16.2-fold higher probabilities of cervical lymph node relapse (P = 0.005 and P = 0.032) and with 16.2- and 8.44-fold shorter disease-free survival (P = 0.009 and P = 0.045). [Conclusions]: Low-grade ILV and VEGF-C expression are independent predictive factors of cervical lymph node relapse and shortening of time to relapse in N0 laryngopharyngeal carcinoma.This work was supported by grants from the Thematic Network for Cooperative Research RESPIRA (Code C003/011; Foundation for Biomedical Research, Hospital Universitario de la Princesa) and the Fondo de Investigaciones Sanitarias (Code FIS 02/1025).Peer Reviewe

Role of intratumoral lymphatic vessels in the lymph node dissemination of laryngopharyngeal squamous cell carcinoma

[Background]: The development of new markers for lymphatic endothelium allowed the study of intratumoral lymphatic microcirculation, as well as its association with lymph node metastasis. [Methods]: In all, 120 patients with laryngopharyngeal squamous cell carcinoma (LPSCC) without previous treatment were retrospectively studied. The immunohistochemical determination of PA2.26 antigen/podoplanin was used to assess intratumoral lymphatic vessels (ILVs) in the primary tumor. [Results]: Multivariate analysis revealed that lymph node metastasis was associated with tumor location (p = .001), differentiation grade (p = .02), and ILV (p = .013). Hypopharyngeal and supraglottic locations, poor grade of differentiation, and ILV, respectively, increased the risk of developing lymph node metastasis 13.5-, 4.7-, 5.2-, and 3.2-fold. [Conclusions]: In our series, the presence of ILV in the primary tumor was an independent risk factor for the development of lymph node metastasis. The incorporation of ILV assessment into routine clinicopathological study might improve the evaluation of patients with LPSCC.Peer Reviewe