| Background:Cervical carcinoma is one of the common gynecological malignancies. Lymph node metastasis is one of the most important biological behaviors of cervical carcinoma including early-stage patients. Lymph node status of cervical carcinoma is the key to determining the prognosis and treatment. It is a hot research on investigating the mechanisms of carcinogenesis, progression and lymph node metastasis of early-stage cervical carcinoma at molecular level in order to look for the way of early diagnosis and treatment.UPP is a highly efficient protein degradation pathway responsible for selective degradation of cytosolic and nuclear proteins. It is thought to be an important target of abnormal regulatory mechanisms of cancer. UbcH10belongs to the E2gene family. As one important member of ubiquitin-proteasome system, it is together with APC/C(E3) and transfers ubiquitin to the specific substrate proteins, makes key mitotic regulators for destruction by the26-S proteasome orderly, and drives progression of cell cycle through mitosis. Recently, aberrantly high UbcH10expression has been demonstrated in a variety of malignancies. In vitro and vivo, the overexpression of UbcH10promoted cell proliferation, invasiveness, and associated with’differentiation, metastasis, apoptosis, cell signaling, and others. Current studies have suggested excessive UbcH10may override the spindle-checkpoint, leading to chromosomal instability, cell cycle disorder, and uncontrolled proliferation,which results in tumorigenesis, invasion and metastasis.Alterations of ubiquitin-proteasome degradation have been reported among other alterations in the processing of MHC class I-associated antigens. Abnormalities of MHC class I and other components occur at a high frequency in human tumors. Tapasin, a48kDa type I transmembrane glycoprotein within ER, forms a large complex with TAP, calreticulin and MHC class I heterodimers and plays a central role in the assembly of MHC class I molecules. Recent researches have indicated that the low express of tapasin exsited in some malignant tumor cells. The downregulation of tapasin is correlated with HLA class I antigen downregulation on the cell surface, and correlated with tumor progression and metastasis in some tumors. But a small number of studies have indicated that tapasin can downregulate the presentation of a certain immunogenic tumor antigen in some cases. In some tumors, tapasin expression did not demonstrate any significant association between tapasin level and the clinical course of the disease.The association of UbcH10with cervical carcinoma has not been reported. Our previous study of screening of gene expression profile has demonstrated tapasin was up-regulated in early-stage cervical squamous cell carcinoma with pevil lymph node metastasis. In our study, we detected the expression of UbcH10and tapasin in normal cervical epithelia and early-stage squamous cervical carcinoma cells to investigate the relationship between UbcH10, tapasin and tumorigenesis, pevil lymph node metastasis of cervical carcinoma.Objective:The objective of our study is to detect the expression of UbcH10and tapasin in normal cervical epithelia and early-stage squamous cervical carcinoma cells and to explore their relationship with tumorigenesis, pelvic lymph node metastasis of cervical carcinoma.Materials and Methods:230Archived formalin-fixed, paraffin-embedded cervical squamous cell carcinoma tissue sections were obtained from the Pathological Department of Women’s Hospital, School of Medicine, Zhejiang University from February2002to July2008. All the patients with Ⅰb-Ⅱa received radical hysterectomy and pelvic lymphadenectomy, and were not treated with chemotherapy, immunotherapy, or radiotherapy before surgery. Among the patients,33cases were with pelvic lymph node metastasis,197cases were without pelvic lymph node metastasis. The complete clinical pathological parameters were collected, including(1)age of the patients,(2)clinical stage,(3differentiation of tumor cells,(4)tumor size,(5)invasion depth of cervical stroma,(6) involvement of lymph-vascular space in parametrial tissue. Another50normal cervical tissue sections were obtained at same period as control. The expression of UbcH10and tapasin were detected by immunohistochemistry. The SPSS statistical software system (Version16.0) was used for statistical analysis. Only results with p <0.05were considered to be statistically significant.Results:1、UbcH10was not expressed in most normal cervical epithelium or with low expression in the basal layer of a small number of cervical squamous epithelium.Expression of UbcH10in early-stage cervical squamous cell carcinoma were higher than that in normal cervical epithelium, and there was significant difference. It was significantly more expressed in poor cell differentiation, deep stromal invasion and parametrial lymph vascular space invasion. Tapasin was not expressed in most normal cervical epithelium or with low expression in the basal layer of a small number of cervical squamous epithelium. Expression of tapasin in early-stage cervical squamous cell carcinoma were higher than that in normal cervical epithelium, and there was significant difference. The expression of tapasin were significantly increase sed in parametrial lymph vascular space invasion.2、In cervical tissue,the expression of UbcH10and tapasin is positively correlated.3、There was significant difference between the expression of UbcH10, tapasin in early-stage cervical squamous cell carcinoma with and without lymph node metastasis. The expression of UbcH10、 tapasin were significantly increasesed in early-stage cervical squamous cell carcinoma with lymph node metastasis.4、Univariate analysis showed that expression of UbcH10, tapasin, age, degree of stromal invasion, lymph vascular space invasion were significantly related with pelvic lymph node metastasis. Multivariate analysis showed that high expression of UbcH10, tapasin, age≤35y, lymph vascular space invasion were independently related to pelvic lymph node metastasis of early-stage cervical squamous cell carcinoma.Conclusions:1、Expression of UbcH10and tapasin in early-stage cervical squamous cell carcinoma were higher than that in normal cervical epithelium, and the high expression of UbcH10were correlated with poor cell differentiation, deep stromal invasion and parametrial lymph vascular space invasion, and the high expression of tapasin were correlated with deep stroma invasion group, which suggested that UbcH10and tapasin were involved in carcinogenesis and progression of cervical carcinoma.2. In early-stage cervical squamous cell carcinoma, high expression of UbcH10, tapasin,age≤35y, lymph vascular space invasion were independently related to pelvic lymph node metastasis. |
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