Tumour expression of lymphangiogenic growth factors but not lymphatic vessel density is implicated in human cervical cancer progression

Abstract

Aims: The aim of the study was to investigate the role of lymphangiogenesis in human cervical cancer progression.

Methods: The expression of VEGF-C, VEGF-D, VEGFR-3, podoplanin (D2-40), LYVE-1 and Prox-1 was studied by immunohistochemistry in 72 cases of invasive squamous cell carcinoma of the uterine cervix. For lymphatic endothelial markers lymphatic vessel density (LVD) was assessed. Correlations with lymphatic vessel invasion, nodal metastases, tumour grade, FIGO stage, and inflammation were also evaluated.

Results: VEGF-D expression significantly correlated with lymph node metastasis, lymphatic emboli and FIGO stage as well as with peritumoural LVD. A marginally significant correlation was also found between the expression of VEGF-C and prognostic parameters. Lymphatic tumour emboli were successfully identified using D2-40 immunohistochemistry and peritumoural D2-40 LVD significantly correlated with lymphatic vessel invasion. However, LVD as assessed by multiple lymphatic markers was not associated with lymphatic metastasis. There was a significant correlation of Prox-1 and LYVE-1 LVD with the inflammatory stromal reaction.

Conclusions: Although LVD as assessed by multiple lymphatic markers was not correlated with prognostic parameters, tumour expression of lymphangiogenic growth factors seems to be critically implicated in lymphatic metastasis and cervical carcinoma progression.