| Cervical cancer (CC) is one of the most common cancer in women, and spreads mainly via the lymphatic system. Although the status of the lymph nodes is not included in the FIGO stage of cervical cancer, the presence or absence of lymph node metastasis provides important prognostic information and influences decision-making for treatment. It is important for gynecologist to learn the status of the lymph nodes accurately in clinical practice. In this study, more than 1300 patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stageâ… A-â…¡B cervical carcinoma and treated mainly with surgery were retrospectively analysed and summarized, while the expressions of some biomolecules in cervical cancer tissues were evaluated by tissue microarray and immunohistochemistical analysis. Through these studies, we aimed to know the frequency of retroperitoneal lymph node metastasis in early stage cervical carcinoma; to definite the indications and clinical significance of systematic retroperitoneal lymphadenectomy and to find some tumor markers for predicting PLN metastasis effectively.Part 1 Analysis of pelvic lymph node metastasis and prognostic factors for 981cervical cancer patients treated mainly with radical surgeryObjective:This study aimed to sum up the clinical characteristics, treatment mode and survival analysis of the patients with cervical cancer treated mainly with radical surgery, and to evaluate the clinical and pathological factors associated with pelvic lymph node (PLN) metastasis and prognosis.Methods:A total of 981 patients with FIGO stageâ… A-â…¡B cervical carcinoma treated with surgery in our hospital were retrospectively analyzed. Using chi-square test and logistic regression model, we analysed the various influence factors for PLN metastasis. Survival analysis was performed by the life table and Kaplan-Meier methods. Multivariate analysis was carried out using the Cox proportional hazard model.Results:229 patients (23.3%) had PLN metastasis. The incidence of PLN metastasis for FIGO stageâ… A,â… B1,â… B2,â…¡A andâ…¡B cervical cancer patients was 0,12.7%,21.6%,26.8% and 31.7%, respectively. Advanced FIGO stage (P= 0.011), pre-treatment anemia (P= 0.007), large tumor size (P< 0.001), lymph vascular-space invasion (LVSI, P< 0.001) and positive parametrium invasion (P< 0.001) were all independent risk factors to predict PLN metastasis. The 5-year overall survival (OS) rate was 84% in all of these patients, and was 100%,92%,85%,81% and 78% for FIGO stageâ… A,â… B1,â… B2,â…¡A andâ…¡B cervical cancer patients, respectively. The patients with no lymph node metastasis had significantly higher 5-year OS rate (89%) than the patients with PLN metastasis (64%, P< 0.001), while there was a better prognosis associated with positive PLN only compared to those with positive common iliac lymph node (P= 0.016). The patients with bilateral PLN metastasis had lower OS rates compare to the patients with unilateral PLN metastasis. The number of lymph nodes involved had no statistically significant differences in OS rates (P= 0.491). Neoadjuvant therapy for the patients with stageâ… B1-â…¡B2 cervical cancer did not improve the survival benefit compared to primary surgery (P= 0.585). Compared to be used alone, the combined use of chemotherapy and radiotherapy could significantly improve the survival rate in the patients with PLN metastasis (P= 0.025). The risk factors including pre-treatment anemia (P= 0.024), non-squamous cell carcinoma (P< 0.001), LVSI (P< 0.001) and PLN metastasis (P< 0.001) were all significant and independent prognostic factors of OS in cervical cancer patients treated with surgery.Conclusion:The patients with FIGO stage IA cervical cancer have no PLN metastasis, and their prognosis are satisfactory. PLN metastasis is one of the independent prognostic factors for cervical cancer patients, and radiotherapy combined with chemotherapy is the appropriate therapy strategy for cervical cancer patients with PLN metastasis. Pre-treatment anemia are not only independent predictors of pelvic lymph node metastasis but also independent prognostic factors for this group of patients.Part 2 Systematic para-aortic lymph node (PAN) dissection and its clinical application in patients with early-stage cervical cancerObjective:This study was to know the frequency and high-risk factors of PAN involvement in early stage cervical carcinoma and to discuss the indications and clinical significance of systematic para-aortic lymphadenectomy.Methods:The clinical and pathological records of 378 patients with FIGO Stageâ… B-â…¡A cervical carcinoma who underwent, from 2007 to 2009, radical hysterectomy and systematic pelvic and para-aortic lymphadenectomy were investigated. The upper limit of the para-aortic dissection was superior to the inferior mesenteric artery (IMA). A receiver operating characteristic curve (ROC curve) was used to determine the tumor size in predicting PAN metastasis. Multiple logistic regression analysis was employed to determine the high-risk factors for PAN metastasis. Life tables, Kaplan-Meier and Cox proportional hazards models were used for survival analyses, while the patients with FIGO stageâ… B-â…¡A in part one study were selected as the control group.Results:The frequency of PAN involvement was 9.3%(35 patients) for all of the 378 patients and was 4A%,7.3% and 12.9% in FIGO stageâ… B1,â… B2 andâ…¡A, respectively. By using the ROC curve, we found the optimal cut off point of tumor size to predict PAN metastasis was 3cm (sensitivity,94.3%; specificity,44.6%). In a multivariate analysis, pre-treatment anemia, tumor size>3cm, lymph vascular space invasion (LVSI) and common iliac lymph node metastasis were independent factors for PAN metastasis. All of the 35 patients with positive PAN involvement had PLN metastasis, but 12 patients (34.3%) had no common iliac lymph node metastasis. The 2-year OS rate and DFS rate for this group of patients were 94% and 88%, respectively. The 2-year DFS for the patients with PAN metastasis was 61%, and PAN metastasis was one of the independent prognostic factors. The survival rate of the patients in this study was not significant improved compared to the patients in part one study with the same stage. While in the patients whose tumor size were equal to or greater than 3cm, systematic PAN dissection significantly improved the DFS rate compared to the control group, and systematic PAN dissection was one of the independent prognostic factors for these patients (P= 0.004).Conclusion:PAN metastasis is common in the patients with FIGO stageâ… B-â…¡A cervical cancer, and it is recommend that systematic para-aortic lymphadenectomy should be routinely done for the patients whose tumor size is equal to or greater than 3cm to improve their DFS rates.Part 3 Expression of Galectin-3,Galectin-7,Cyclin B1 and c-myc in cervical cancer and their relationship with lynph node metastasisObjective:This study was to evaluate the expression of Galectin-3 (Gal-3),galectin-7 (Gal-7),Cyclin B1 and c-myc proteins in cervical cancer tissues and their correlation with PLN metastasis.Methods:174 patients with FIGO stageâ… /â…¡cervical carcinoma undergoing radical surgery were selected, and their cervical cancer tissues were collected. The expression of Gal-3,Gal-7,Cyclin B1 and c-myc proteins in cancer tissues were semi-quantitatively tested by tissue microarray and immunohistochemistical analysis. Then the correlations between the expression of the four proteins and the clinicopathological parameters of these patients were evaluated.Result:The positive expression rate of Gal-3,Gal-7,Cyclin B1 and c-myc was 54.0%,52.3%,51.1% and 56.3%, respectively in the cervical cancer tissues. The expression of these four proteins were all positively correlated with deep-muscle invasion. Using chi-square test, we found that Gal-3,Gal-7 and Cyclin B1 were all significant associated with PLN metastasis, while the multivariate analysis revealed that the positive expression of Gal-3 (P= 0.015) and Cyclin B1 (P= 0.038) were both the independent risk factors for predicting PLN metastasis. The sensitivity rate for detecting metastatic PLN was 92.3% (36/39) when the combined measurement of Gal-3 and Cyclin B1 was applied. The positive expression of Gal-3 (P=0.013),Cyclin B1 (P= 0.006) and c-myc (P< 0.001) were all significantly correlated with poor overall survival, while c-myc protein expression was one of the independent prognostic factors for these patients.Conclusion:Positive expression of Gal-3 and Cyclin B1 proteins are independent predictive factors for PLN metastasis, and the combined detection of these two proteins could sensitively to predict PLN metastasis in patients with cervical cancer. Positive expression of c-myc protein is one of the independent prognostic factors in patients with cervical cancer.
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