Expression Of VEGF-C And COX-2 In Cervical Cancer And Its Clinical Significance

Objective Cervical cancer is the commonest malignant tumor of gynecological cancers, which seriously threaten the health of most women. As other malignant tumor, distant metastasis usually causes death of patients with cervical cancer, and metastasis of lymph node is the key to decide prognosis and design the treatment strategy of patients with cervical cancer.Therefore, the effective approach of prevention and treatment plays an important role in improving prognosis of cervical cancer. Recent research shows that the formation of blood vessel and lymphatic vessel is correlated with the growth and metastasis of tumor, therefore, the study on regulating the formation of blood and lymphatic vessel in tumor is becoming one of new hotspot.Familial members of vascular endothelial growth factor(VEGF) have important effect on the growth and metastasis of tumor. Vascular endothelial growth factor C(VEGF-C) is a kind of new homologue of VEGF, which is the highest specific stimulating-growth factor of lymphatic endothelium so far. VEGF-C can modulate the formation of new blood and lymphatic vessel, promote the growth of the tumor cell, suppresse the apoptosis of tumor cell, and induce metastasis by lymphatic system.Cyclooxygenase-2(COX-2) is an important rate-limiting enzyme for the synthesize of prostaglandins. COX-2 play a role in oncogenesis and progression by enhancing angiogenesis, suppressing cell apoptosis andincreasing invasive ability of tumor cells.Recent research implies that COX-2 promote formation of lymphatic vessel possibly through mediating up-regulation of VEGF-C expression. However, the relationship between VEGF-C and COX-2 in cervical cancer has not been reported. In the present study, we detected the expression of VEGF-C and COX-2 in normal cervix and cervical cancer by immunohistochemical method, analyzing their correlation, combining with patho-clinical data, try to explore the role of VEGF-C and COX-2 in the oncogenesis progression,invasion and metastasis of cervical cancer, hoping to provide new thought for the prognosis judgement and clinical treatment of cervical cancer. Materials and Methods76 Cervical cancer samples were collected from the department of Gynecology in the First Affiliated Hospital of Zhengzhou University from January 2001 to March 2003,with complete clinical data. Samples of Stage I and stage II were obtained from tissues of resection ; samples of Stage IIIand stage IV were obtained from tissues of biopsy. In addition, histologically normal cervical tissue samples were obtained from other patients (n = 21) with uterine benign lesions by a total hysterectomy. Cervicitis cases were excluded in the study. The mean age of the patients was 50.21 ± 12.76 (range, 33 to 77) years. According to FIGO clinical stages in 1995, among them 22 cases were stage I ,39 cases were stage II, 9 cases were stage III, 6 cases were stage IV. The positive group of lymph node metastasis were composed of 28 cases and the negative group of lymph node metastasis were composed of 48 cases. Histological type: squamous carcinoma 60 cases, adenocarcinoma 14 cases, adenosquamous carcinoma 2 cases. Histological grade of squamous carcinima: well differentiation (G1) 19 cases, moderate differentiation (G2) 23 cases, poor differentiation (G3) 18 cases. All tissues were pathologically confirmed and no patient had received radiotherapy, chemotherapy, or other biological therapy before excision. All the specimens were fixed with formalin and embedded routinely with paraffin, the thickness for every section was 4μm. SP immunohistochemistry method was used to detect the expression of VEGF-C and COX-2 in 76cases of cervical cancer and 21cases of normal cervix. SPSS10.0 software was used to analyze the data, a=0.05 wasconsidered the level of significance.Results1. The expression of VEGF-C was negative in normal cervical tissues, the expression rate of VEGF-C was 46.05% (35/76) in cervical cancer tissues, there was statistical significance for the VEGF-C expression rate in those two groups (P<0.01). The expression of COX-2 was negative in normal cervical tissues; the expression rate of COX-2 was 36.84% (28/76) in cervical cancer tissues, there was statistical significance for the COX-2 expression rate in those two groups (P<0.01).2. The positive expression rate of VEGF-C in stage I, stage II and stage III~IV of cervical cancer were respectively 27.27%(6/22), 46.15%(18/39), 73.33%(11/15), there was statistical significance among those three groups (P<0.05). The positive expression rate of COX-2 in stage I, stage II and stage III-IV of cervical cancer were respectively 27.27%(6/22), 35.90%( 14/39), 53.33%(8/15), there was not statistical significance among those three groups (P>0.05).3. The positive expression rate of VEGF-C in well, moderate and poor differentiation of squamous carcinoma were respectively 26.32%(5/19), 34.78%(8/23), 66.67%(12/18), there was statistical significance among those three groups(P<0.05). The positive expression rate of COX-2 in well, moderate and poor differentiation of squamous carcinoma were respectively 47.37%(9/19), 26.09%(6/23), 11.11%(2/18), there was statistical significance among those three groups(P<0.05).4. The positive expression rate of VEGF-C in lymph node metastasis group (67.86%) was obviously higher than that in lymph node negative group (33.33%),there was statistical significance(P<0.05). The positive expression rate of COX-2 in lymph node metastasis group (64.29%) was obviously higher than that in lymph node negative group (20.83%), there was statistical significance (P<0.05).5. The positive expression rate of VEGF-C (62.5%) in cervical adenocarcinomas was a little higher than that (41.27%) in squamous carcinoma of cervix, but there was notstatistical significance between them (/><0.05).The positive rate of COX-2 (68.75%) in cervical adenocarcinoma was obviously higher than that (28.33%) in squamous carcinoma of cervix, there was statistical significance between them (P<0.05).6. The expression of VEGF-C was positively correlated with the expression of COX-2 in cervical cancer (r =0.484, P<0.01).conclusions1. No VEGF-C expression showed in normal cervix tissues, but overexpression in cervical cancer. The expression level of VEGF-C was correlated with pelvic lymph node metastasis,clinical stage and histological grade of cervical cancer, indicating that VEGF-C might play an important role in carcinogenesis, development, invasion and metastasis of cervical cancer, it could be hopefully a marker to evaluate the prognosis of cervical cancer.2. No COX-2 expression showed in normal cervix tissues, but overexpression in cervical cancer. The expression level of COX-2 was correlated with pelvic lymph node metastasis, histological type and histological grade of cervical cancer, indicating that COX-2 could take part in carcinogenesis of cervical cancer, and it might be correlated with the invasion and metastasis of cervical cancer.3. The expression of VEGF-C is correlated with that of COX-2 in cervical cancers, this implies COX-2 and VEGF-C may cooperatively take part in the occurrence, invasionand metastasis of cervical cancer.