| [Background] Cervical cancer is a worldwide health problem. It is the second most frequent cancer among women after breast cancer. Lymph node metastasis is the most common spreading way, and is the most important prognostic factor. But the mechanism of lymph metastasis is not clear. Thus we try to probe the field through two ways. First, we investigated if tumor lymphangiogenesis is associated with lymph node metastasis of cervical squamous cell carcinoma (SCC). Second, we investigated wheather CXCR4/ SDF-1α axis has a role in lymph node metastasis of cervical SCC. The aim is to find a pboble new route inhibiting lymph node metastasis.Part OneTumor Lymphangiogenesis and its clinical significance in cervical Squamous Cell CarcinomaObjective To investigate the clinical significance of lymphangiogenesis in cervical cancer. Methods Lymphotic microvessels wereimmunostained by the lymphatic marker Podoplanin, and quantified using computer-assisted morphometric analysis in introtumor and peritumor area in 35 cervical cancer specimens of stage Ib,IIa. The association with clinicopathologic data was analyzed. Results (DLymphatic microvessels were larger and denser in the peritumor than the intratumor. Cancer cells in the intratumoral lymphatic vessels were found in lymph metastatic patients.(2) Lymphatic vessels density(LVD) in the peritumor was (31 ± 10)vessels/mm^,and LVD in the intratumor was (20+ 10)vessels/ mm2(PO.01).Relative lymphatic vessel area(LVA) was 0.75%±0.40%,and LVA in the intratumor was 0.19 + 0.1 l(P<0.01).(3). Intra- and peri-tumoural LVD and LVA in patients with lymph node metastasis were (29 + 7)vessels/ mm" , (40 + 5)vessels/mm2,0.27%±0.10%, 1.23%±0.36%,respectively, and those without lymph node metastasis were (16±8) vessels/ mm2 ,(28 + 9) vessels/ mm2, 0.16%± 0.09%,0.56%±0.20% (PO.01, <0.01, <0.05, <0.01).(4) Peri-tumoural LVA and intra-tumoural LVD,LVA in patients with histologic grade K IL III were 0.42% + 0.10%, (9±3)vessels/mm2, 0.06%±0.04%, 0.77%±0.37%, (21 ±8) vessels/mm2, 0.21% + 0.09%, 0.83% ±0.46%, (22 ±11) vessels/ mm2, 0.21% ± 0.12% respectively.There were statistic significances between grade II, III and grade I,no statistic significances between grade II and III. Conclusion Higher lymphangiogenesis in early cervical squamous cell cancer may be associated with the risk of lymph node metastasis.Part TwoStudy on CXCR4/ SDF-la axis in lymph node metastasis of cervical squamous cell carcinoma[Abstract] Objective To investigate the expression of CXCR4 and SDF-la in tissues of cervical cancer and normal cervix, Hella cells and lymph nodes respectively, and the effect of CXCR4/ SDF-la on metastasis of cervical cancer cells. Methods Cervical squamous cell cancer (SCC) tissues (n=35), normal cervical tissues (n=10), metastatic (n=10) and nometastatic lymph nodes (n=50), and Hella cells were immunohistochemically stained with mouse anti-CXCR4 monoclonal antibody (mAb). Meanwhile, lymph nodes were immunohistochemically stained with rabbit anti-SDF-la. In vitro invasion of Hella cells was evaluated using Transwell Permeable Supports, in which Hella cells with/without CXCR4 mAb pre-incubation were seeded in the upper chambers, medium containing 0-100ng/ml of SDF-la was added to the lower compartments. For evaluating the effect of CXCR4/ SDF-la on proliferation of cervical cancer cells, Hella cells were cultured for 72 hours exposed to SDF-la with and without CXCR4 mAb. Results CXCR4 was expressed on SCC cells in all cervical cancer, metastatic lymph node and Hella cells, but not in normal cervix. SDF-la was expressed on lymph cells in all lymph nodes. SDF-la induced the directed migration of Hella cells with a concentration-depended model, which was inhibited by using CXCR4 mAb. SDF-la also stimulated the proliferation of Hella cells mediated by CXCR4. Conclusion CXCR4/ SDF-la axis probablyparticipates in the metastasis towards lymph nodes in cervical cancer.
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