Abstract:
In many human malignant tumors the lympho-vascular metastasizing represents the main
way of tumor-modified cells spreading. Lymphatic vessels invasion by the neoplastic cells leads to
the involvement of regional lymph nodes (RLN) in tumor process. It is well known that metastatic
damage of RLN correlates with poor outcome. Tumor cells secrete biological active substances that
lead to the appearance of newly formed blood network which keeps up the metabolic activity inside
the tumor. Tumors also produce growth factors for lymphatic endothelial cells. Until now it is not
clearly established, tumor cells invade the preexistent peripheral lymphatic vessels or invade the newformed vessels which are formed during tumoral lymphangiogenesis. To establish the origin of
lymphatic vessels (LM) involved in metastatic spreading of neoplastic cells in squamous cell
carcinoma (SCC) of the uterine cervix. There were investigated the postoperative material taken from
patients with SCC of the uterine cervix (n=39). All material was stained with hematoxylim Harris and
eosin. For immunohistochemical (IHC) procedure were selected only the cases with intravascular
tumor emboli (n=30). Two monoclonal antibodies were used: anti D2-40 (RTU clone,
DakoCytomation, Denmark) to highlight the LV and anti Ki-67 (DakoCytomation Carpinteria, CA,
USA) for identification of proliferated endothelial cells. The IHC reaction was performed in
accordance with Avidin-Biotin technique (LSAB+/Double Stain). Nuclei were stained with Lillie’s
modified Hematoxylin. The entire IHC procedure was performed with DakoCytomation Autostainer. There were counted only the LV with the tumor emboli inside. The LV which were positive only for
anti D2-40 were considered to be the preesisting vessels, and that LV which were positive for both of
the antibodies were considered to be the newly-formed, tumor-derived vessels. LV were found in
intratumoral and peritumoral areas. All intratumoral LV were small and flattened, without lumen.
Lymphatics placed at the periphery of tumor nests were relatively large and perfusable (with well
distinguished lumen). There were found 24 lymphatics with emboli inside. All of them were placed in
the peritumoral area. Were detected 11 (45,83%)LV with proliferated endothelial cells. Size of
proliferated LV were smaller than size of preexisting lymphatics. There were not found any
correlation between the distance of proliferated and preexisting LV from the invasive front of the
tumor. Relatively few studies addressed to lymphangiogenesis in neoplastic lesions of the uterine
cervix. From them, some addressed to the prognostic value of the lymphovascular invasion in relation
with lymph node status and systemic metastasis. It was found that metastases is significantly higher in
patients with lymphovascular invasion than in cases without, as otherwise expected. D2-40 is a
specific and the most sensible marker for lymphatic endothelial cells. Ki-67 is a nuclear marker which
is positive in dividing cells. LV with metastatic emboli were found only at the periphery of the tumor
mass. These data show that peritumoral LV are involved in metastatic spreading of tumor cells.
Formation of new LV begins with proliferation of their endothelial cells. We use Anti Ki-67 to
highlight these mitotically active cells. The size of LV with Ki-67 positive cells were smaller than the
size of preexisting LV, which shows that these lymphatics are younger. The high amount of newlyformed LV with emboli inside proves that tumor derived lymphatics participate in metastatic
dissemination. Conclusions. 1) Lymphovascular metastasizing in squamous cell carcinoma of the
uterine cervix occurs through peritumoralLV 2) neoplastic cells disseminate either through
preexisting LV and newly-formed.
