Clinical Study Of TROP2、KI67 Expression In Cervical Lesions

Cervical cancer is the third most prevalent malignancy amongwomen worldwide, with an estimated approximately 530000new cases and 275,000 women death each year. Trophoblast cell surface antigen 2 (TROP2) is a 36 kDa transmembrane glycoprotein belonging to tumor-associated calcium signal transducer (TACSTD) gene family. It was originally identified in human trophoblast cell lines, and elevated expression was found in various types of epithelial carcinomas while low or restricted expression was found in normal tissues. Overwhelming evidence has demonstrated that the aberrant expression of the human trophoblast cell-surface antigen (TROP2) was associated with tumor aggressiveness and poorprognosis in a variety of human cancers. TROP2 may represent a prospective prognostic indicator and a potential therapeutic target of cervical cancer,but the specific mechanism still needs further study. The development of tumor is closely related to cell proliferation, as a nuclear antigen, Ki67 is associated with cell proliferation, which was recognized to be more accurate, reliable, ideal marker for detecting cell proliferation activity. Currently the clinical study about relationships betweenTROP2、Ki67 and cervical lesions has not been reported. In this treatise,the TROP2 and Ki67 expressionwas detected by immunohistochemistry、RT-qPCR and Western Blotting in SCC and CIN and its relationship with clinical pathology was Investigated.OBJECTIVEThe purpose of this study was to evaluate the expression of TROP2、Ki67 expression in squamous carcinoma of cervix (SCC) and cervical intraeptithelial neoplasia (CIN) and normal cervical epithelia(NCE). To explore the clinical pathological significance and correlation of TROP2 and Ki67.METHODSWe detected the expression of TROP2 and Ki67 in 22 cases of normal cervix,35 cases of CIN Ⅰ、 35cases of CIN Ⅱ、 38 cases of CINⅢ and 65 cases of SCC by immunohisto chemical SP assay, and analyzed the relationship between the expression and clinicop athological characteristics. Fluorescence quantitative rewerse transcription(RT) PCR were used to detect 20 cases of normal cervix、20 cases of CIN Ⅰ、20cases of CIN Ⅱ、 20 cases of CINⅢ and 20 cases of SCC TROP2、Ki67 mRNA expression.Western blot were used to detect 20 cases of normal cervix、20 cases of CIN Ⅰ、 20cases of CIN Ⅱ、 20 cases of CINIII and 20 cases of SCC TROP2 protein expression.RESULTS1IHC results①the expression of TROP2 protein in SCC and CIN was located on the cell membrane. The positive ratio of TROP2 in NCE. CIN and SCC was 22.7%,72.4%,95.4%. Expression rate in SCC and CIN were obviously higher than that in control group, there were significant differences (p<0.001); The positive ratio of TROP2 inCIN Ⅰ、 CIN Ⅱ、 CINⅢwas 52%.71.4%. 86.8%, there were significant differences (p<0.001). TROP2 expression levels were significantly different between groups in regards to histological grade,histological-subtype and lymphatic metastasis (p<0.05). However, there was no significant associations between the expression of TROP2 and age, tumor size(p>0.05).②The expression of Ki67 protein in CC and CIN was located on the nucleus. The positive ratio of Ki67 in SCE. CIN and SCC was 9.1%.62.2%.90.9%. Expression rate in SCC and CIN were obviously higher than that in control group, there were significant differences (p<0.001); The positive ratio of Ki67 inCIN Ⅰ、 CIN Ⅱ、 CINⅢwas 36%.62.8%.78.9%, there were significant differences (p<0.001). Ki67 expression levels were significantly different between groups in regards to histological grade,histological-subtype and lymphatic metastasis (p<0.05). However, there was no significant associations between the expression of Ki67 and age, tumor size(p>0.05).③There was positive correlation between the expression of TROP2 and KI67 in normal cervix、CINⅠ、CIN Ⅱ、 CINⅢ and SCC. (p<0.01)2. RT-qPCR results②The relative mRNA expression levels ofTROP2 in normal cervix. CIN Ⅰ. CIN Ⅱ. CINⅢ and CC was 0.97±0.11、1.09±0.17、1.26±0.14、1.51±0.10、1.93±0.17. The relative mRNA expression levels ofTROP2 in CIN Ⅱ、 CINⅢ and CC was significantly higher than that in normal cervix (p<0.05)②The relative mRNA expression levels of KI67 in normal cervix. CIN Ⅰ. CIN Ⅱ. CINⅢ and CC was 0.93±0.12、1.16±0.08、1.59±0.12、1.94±0.25、2.32±0.14. The relative mRNA expression levels of KI67 in CIN Ⅱ、 CINⅢ and CC was significantly higher than that in normal cervix (p<0.01).3 The western blotting results showed that the TROP2 relative protein expression levels in normal cervix. CIN Ⅰ、 CIN Ⅱ、 CINⅢ and CC was 1.0±0.03、1.15±0.12、1.47±0.11、1.79±0.12. 2.06±0.11. The TROP2 relative protein expression levels in CIN Ⅰ、CIN Ⅱ、 CINⅢ and CC was significantly higher than that in normal cervix (p<0.01)CONCLUSIONS1.The present study suggest that the overexpression of TROP2 may play crucial roles in the development and pathogenesis of squamous carcinoma of cervix. The exprssion of TROP2 was correlated with clinical stages, metastatic lymph node of SCC, but was uncorrelated with age and tumor size.TROP2 may represent a prospective prognostic indicator and a potential therapeutic target of cervical cancer.2.The overexpression of Ki67 may play crucial roles in the development and pathogenesis of squamous carcinoma of cervix. The exprssion of Ki67 was correlated with clinical stages, metastatic lymph node of SCC, but was uncorrelated with age and tumor size. Detection of the expression of Ki67 is provided with important clinical applied value in understand the biological behavior and estimation prognosis of SCC.3.There was positive correlation between the expression of TROP2 and KI67 in normal cervix、 CEN Ⅰ、 CINⅡ、 CINⅢ and SCC. Detection of TROP2 and KI67 expression will be the decision of the malignant and prognosis of SCC.