OBJECTIVES: In this study we have tested a potential role of the LEDGF–VEGF-C axis in VEGF-C tumor induced lymphangiogenesis, possibly represented by high peritumoral lymphatic vessel density (LVD), which may be one of the mechanisms leading to lymphatic space invasion (LSI) and metastatic spread of squamous cell cervical cancer. MATERIAL AND METHODS: The clinical data for this study were collected from 99 patients diagnosed with squamous cell cervical carcinoma from January 1995 to December 2005 who underwent standard surgical approach consisted of hysterectomy followed by bilateral pelvic lymphadenectomy at the Department of Obstetrics and Gynecology - Clinical Hospital Center of Rijeka, Croatia. Formalinfixed, paraffin-embedded specimens, from 99 patients were analyzed at the Department of Pathology, School of Medicine, University of Rijeka, Croatia. Tissue sections of primary tumors and its lymph node metastases were examined by immunohistochemistry for LEDGF, VEGF-C expression and LVD using three primary antibodies LEDGF, VEGF-C and D2-40. For immunoreactivity score we have used the staining intensity and the percentage of stained tumor cells. LVD was calculated as a mean value of lymphatics counted in peritumoral area. Results were assigned by using a mean value of expression and divided in two groups according to lymph node status. RESULTS: Lymph nodes metastasis were positive in 21 (21,1%) patients with squamous cell carcinoma of the uterine cervix and overall survival rate was 81,8%. VII The expression levels of LEDGF were significantly higher in the lymph node positive group (mean immunostaining scores were 190,6 and 170,7; P < 0,04). The mean immunostaining VEGF-C scores were 126,3, for lymph node positive group and 109,3 for lymph node negative group. The peritumoral LVD, within 1 mm from the tumor edge, was significantly higher between two study groups according to lymph node status. High peritumoral LVD showed significant correlation with lymph node metastasis. Lymphatic space invasion stained with D2-40 (LSI) was discovered in 53,5% patients. VEGF-C showed increased expression and correlated with high peritumoral LVD (p=0,05), and lymph node metastasis (p=0,03). LEDGF showed increased expression, but without correlation with high peritumoral LVD, or lymph nodal metastasis. In multivariate analysis by logistic regression, VEGF-C expression was independent prognostic factor for lymph node metastasis, while LSI was an independent prognostic factor for recurrent disease and survival in cervical cancer. LEDGF, VEGF-C expression and peritumoral LVD had no sigificance as an independent predictors for recurrent disease and survival in cervical cancer. CONCLUSIONS: Our findings suggest a potential role of the LEDGF–VEGF-C axis in VEGF-C tumor- induced lymphangiogenesis, represented by high peritumoral LVD, which may be one of the mechanisms leading to lymphatic invasion and metastatic spread. In multivariate analysis by logistic regression, VEGF-C expression was independent prognostic factor for lymph node metastasis while, LSI was an independent prognostic factor for recurrent disease and survival in cervical cancer. LEDGF, VEGF-C expression and peritumoral LVD had no sigificance as an independent predictors for recurrent disease and survival in cervical cancer.