Lymph Node Involvement in Early-Stage Cervical Cancer: Is Lymphangiogenesis a Risk Factor? Results from the MICROCOL Study

SIMPLE SUMMARY: The prognosis of cervical cancer is significantly influenced by lymph node involvement. The lymphatic system is the primary way of metastasis for cervical carcinoma, and lymph-vascular space invasion (LVSI) is considered the most important risk factor for pelvic lymph node metastasis (PLNM). Previous studies have not clarified the correlation between lymphangiogenesis and an increased risk of metastasis and tumor recurrence. The evaluation and identification of several markers of lymphangiogenesis may identify patients with high risk of PLNM. Our findings suggest that the lymphatic spread does not required the proliferation of new lymphatic endothelial cells. These results emphasize the importance of pre-existing peritumoral lymphatic vessels in the metastatic process in early cervical cancer. ABSTRACT: Background: In patients with cervical cancer, the presence of tumoral lymph-vascular space invasion (LVSI) is the main risk factor for pelvic lymph node metastasis (PLNM). The objective of this study was to evaluate the presence of several markers of lymphangiogenesis in early-stage cervical cancer and their correlation with PLNM and tumoral recurrence. Materials and Methods: Seventy-five patients with early-stage cervical carcinoma underwent sentinel lymph node (SLN) sampling in association with complete pelvic lymph node dissection. Primary tumors were stained with the following markers: Ki67, D2-40, CD31 and VEGF-C. A 3-year follow-up was performed to evaluate the disease-free survival. Results: Overall, 14 patients (18.6%) had PLNM. Positive LVSI was seen in 29 patients (38.6%). There was a significant correlation between LVSI evidenced by H/E staining and PLNM (p < 0.001). There was no correlation between high Ki67, CD31, D2-40, and VEGF-C staining with PLNM or tumor recurrence. Conclusions: Our data support that lymphatic spread does not require the proliferation of new lymphatic endothelial cells in early-stage cervical cancer. These results emphasize the importance of pre-existing peritumoral lymphatic vessels in the metastatic process in early cervical cancer. None of the markers of lymphangiogenesis and proliferation assessed in this study were predictive of PLNM or recurrence.