Expression And Clinical Significance Of Heparanase In Metastatic Lymph Nodes Of Cervical Squamous Carcinoma

Background and0bjectiveCervical cancer is one of the common gynecologic malignancy. Theepidemiological survey showed an upward trend in the incidence and a serious threatto the woman ’s life. The cause of cervical cancer at the head of female cancer death.The clinical treatment failure and the cause of death of tumor is invasion andmetastasis. Lymph node metastasis is the most common way of cervical cancer. It isan important factor to clear and predict the prognosis of cancer.Tumor invasion and metastasis is determined by a variety of biological behaviorof tumor cells. The important aspect of these behavior including tumor cellsdegradation to their surrounding matrix protein. Heparanase is an glucuronidaseendonuclease, it can degrade the heparan sulfate at several sites and destruct theintegrity of extracellular matrix and basement membrane. Thus contributing to tumorcells through the extracellular matrix and the vascular wall and promote local tumorinvasion and metastasis. Our previous studies and some abroad studies haveconfirmed the significantly higher expression of HPA in primary foci of cervicalcancer. It is an important biomarker for cervical cancer. Cytokeratin19is a smallestmember of the cytokeratin family and express in the range of rigorous, which is one of the important proteins can make up the skeleton of squamous cells. It isspecifically expressed in the female reproductive tract epithelium, and become moresensitive and specific marker in cells epithelial tumors.Domestic and foreign are looking for specificity and sensitivity of biomoleculesindicators in lymph node metastasis. If they can accurately predict lymph nodemetastasis in the preoperative, then can accurately understand the scope of the tumor,choose the right treatment plan. However, the effective means of diagnosis in lymphnode metastasis is still lack. This study is based on the relationship between HPA andcervical cancer or HPA and lymph node metastasis. HPA was detected in cervicalsquamous carcinoma with metastatic lymph nodes and primary foci byimmunohistochemical SP in this study. Analyze the relationship between HPAexpression and clinical prognostic factors for the first time, in order to provide a newmolecular target in diagnosis of metastatic lymph nodes in cervical squamous cellcarcinoma.Materials and Methods102cases of paraffin embedded blocks of cervical squamous cell carcinomawere obtained from January2007to December2012at Department of Pathology, theSecond Affiliated Hospital of Zhengzhou University, including53cases of cervicalsquamous carcinoma with metastatic lymph nodes diagnosed through routinepostoperative pathology（group A）,49cases of cervical squamous carcinoma withoutmetastatic lymph nodes（group B）. The primary foci, metastatic lymph nodes andnon-metastatic lymph nodes in group A were selected for immunohistochemicalstaining; primary foci and non-metastatic lymph nodes in group B were selected. Allparaffin embedded blocks tested in study were performed HE staining. The blocks ofHPA positive expression were performed CK19immunohistochemical staining, toconfirm if the lesion is the focus of cervical carcinoma metastasis. Image analysistechnique was used to measure average gray value of the expression of HPA, thencalculating the positive units of HPA expression.The data were analyzed by SPSS17.0statistical software,x±s for the image morphometry data. χ2testing for the qualitative data of groups and HPA expression.Survival rates were calculated by the Kaplan-meier method, and differences wereexamined by the Log-rank, multivariate analysis using Cox regression analysis.Inspection level is α=0.05.Results1. HPA expression of the metastasis lymph node for routine postoperativepathological diagnosis in group A: Positive rate of HPA in group A was90.6%（48／53）both in primary foci and metastatic lymph nodes,13.2%（7／53）in non-metastaticlymph nodes for routine postoperative pathological diagnosis. HPA average grayvalue increased gradually from primary foci to metastatic lymph nodes tonon-metastatic lymph nodes with significant difference in group A（F=30.521，P=0.000）. In contrast with the gray value, HPA positive unit decreases gradually (F=6.351，P=0.021).2. HPA expression of the without metastasis lymph node for routine postoperativepathological diagnosis in group B: Positive rate of HPA in group B was81.6%（40／53）in primary foci,10.2%（5／49）in non-metastatic lymph nodes. HPA average grayvalue in primary foci was significantly lower than that in lymph nodein group B（F=21.397，P=0.000）. HPA positive unit Primary foci was significantly higher than thelymph node（F=4.827，P=0.037）in group B.3. Relationship between the expression of HPA in cervical squamous carcinomaand the clinicopathologic feature of carcinoma: HPA expression was significantlycorrelated with three clinicopathologic parameters, clinical stage（P=0.000）,histological differentiation（P=0.000）, and lymph node metastasis（P=0.000）.4. The relationship between expression of HPA in cervical squamous carcinomaand survival: as Kaplan-Meier survival analysis showed, the median overall survivaltime of all patients was（MOS,49.0±2.9）months. MOS of patients with lymph nodemetastasis（36.0months）is significantly lower than MOS of patients without lymphnode metastasis（58.5months）, P=0.023; MOS of patients with positive HPAexpression in lymph nodes（38.5months）was significantly lower than MOS of patients with negative HPA expression in lymph node（s57.0months）, P=0.040. Coxregression analysis showed that lymph node metastasis is an independent risk factorin prognosis of cervical cancer （P <0.05）.Conclusions1. HPA expression both in primary foci and metastatic lymph nodes of cervicalsquamous carcinoma was increased significantly. lymph node metastasis is anindependent prognostic factor for cervical cancer. So HPA is an important biomarkerfor cervical cancer.2. MOS of the patients of cervical squamous carcinoma with lymph nodemetastasis is significantly lower than MOS of the patients without lymph nodemetastasis. MOS of the patients of cervical squamous carcinoma with HPA positivelymph nodes was significantly lower than MOS the patients with HPA negativelymph nodes, indicating that patients with HPA positive lymph nodes have the pooroutcome.