VEGF-C and lymphatic vessel density in oral squamous cell carcinoma: association with occult lymph node metastases and patients' prognosis

• Grant number: 07/04907-0
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): December 01, 2007
• Effective date (End): November 30, 2010
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal researcher: Denise Tostes Oliveira
• Grantee: Simone Eloiza Sita Faustino
• Home Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil

Abstract

The metastatic dissemination of head and neck squamous cell carcinoma (HNSCC) to neck lymph nodes occurs rather through the lymphatic system. Furthermore, it has long been established that the presence of lymph node metastasis (pN+), verified through histopathological analysis, is the most important prognostic factor to the patients with HNSCC. Recent studies reported that the vascular endothelial growth factor C (VEGF-C) may directly induces lymphangiogenesis and dilatation of lymphatic vessels in solid tumors of different sites. However, the VEGF-C and its correlation with the lymphatic vessel density has not been frequently studied in oral squamous cell carcinoma (OSCC). The aim of this study is: (1) to evaluate the peri and intratumoral lymphatic vessel density using podoplanin antibody; (2) to correlate the lymphatic vessel density and the VEGF-C expression, as described previously by Faustino, S.E.S (2007); (3) to verify the lymphatic vessel density and its correlation with the occurrence of occult metastasis in neck lymph nodes and with the patients’ prognosis with OSCC. A total of 87 cases of surgically excised primary oral squamous cell carcinoma with clinical stages I and II (located in tongue and floor of the mouth) from the files of Head and Neck Surgery and Otohinolaryngology Department of the A. C. Camargo Cancer Hospital, São Paulo, Brazil, from 1968 to 2001, studied previously by Faustino, S.E.S (2007), will be analyzed. Clinical information regarding the gender, age, race, tobacco and alcohol abuse, localization, stage by the TNM/UICC, treatment, lymph nodes involvement, local and cervical recurrences, distant metastasis and second primary tumors were obtained from the patients’ files. In addition, the immunohistochemical study will be performed on paraffin sections of OSCC with monoclonal podoplanin (specific for lymphatic vessel) using a standard streptavidin-biotin-peroxidase technique. The peri- and intratumoral lymphatic vessel density immunostained with podoplanin will be analysed using a camera attached to a light microscope and a specific computer image software. The correlation among the lymphatic vessel density on the OSCC and: (1) VEGF-C expression; (2) clinical and microscopic variables; (3) histopathological malignancy grading and (4) occurrence of occult lymph node metastases will be obtained by chi-square test or Fisher exact test. The 5 and 10-year survival rates will be calculated by the Kaplan-Meier method and compared by log-rank test. P values less than 0.05 will be considered statistically significant. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ALMEIDA, AROLDO DOS SANTOS; OLIVEIRA, DENISE TOSTES; PEREIRA, MICHELE CONCEICAO; SITA FAUSTINO, SIMONE ELOIZA; NONOGAKI, SUELY; CARVALHO, ANDRE LOPES; KOWALSKI, LUIZ PAULO. Podoplanin and VEGF-C Immunoexpression in Oral Squamous Cell Carcinomas: Prognostic Significance. ANTICANCER RESEARCH, v. 33, n. 9, p. 3969-3976, SEP 2013. Web of Science Citations: 10.

CAETANO, ADRIANA DOS SANTOS; TJIOE, KELLEN CRISTINE; SITA FAUSTINO, SIMONE ELOIZA; COSTA HANEMANN, JOAO ADOLFO; FERNANDES BELONE, ANDREA DE FARIA; SOARES, CLEVERSON TEIXEIRA; OLIVEIRA, DENISE TOSTES. Immunolocalization of podoplanin in benign odontogenic tumours with and without ectomesenchyme. ARCHIVES OF ORAL BIOLOGY, v. 58, n. 4, p. 408-415, APR 2013. Web of Science Citations: 11.

OLIVEIRA, D. T.; BIASSI, T. P.; FAUSTINO, S. E. S.; CARVALHO, A. L.; LANDMAN, G.; KOWALSKI, L. P. Eosinophils may predict occult lymph node metastasis in early oral cancer. CLINICAL ORAL INVESTIGATIONS, v. 16, n. 6, p. 1523-1528, DEC 2012. Web of Science Citations: 10.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FAUSTINO, Simone Eloiza Sita. VEGF-C e densidade de vasos linfáticos em carcinoma espinocelular de boca: associação com as metástases linfonodais ocultas e com o prognóstico dos pacientes. 2010. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Odontologia de Bauru Bauru.