Expression Of Ki-67 And PCNA And Their Association With HPV In CIN And Early-stage Cervical Cancer

Objective:To investigate the expression , biological significance and diagnostic value of Ki-67 and PCNA and their association with HPV infection in early-stage cervical carcinoma and the cervical intraepithelial neoplasia.Methods:18 cases of early-stage cervical cancer (8 cases of stage I and 10 cases of stage IIA included),37 cases of cervical intraepithelial neoplasia (20 CINI/LSIL and 17 CINII/III/HSIL included) and 15 cases of cervicitis were introduced into the study. The immunohistochemical staining(S-P method) was used for Ki-67 and PCNA expression detection. HPV was tested by PCR method (premier set MY09/11) and compared part of the results with HCII results of 33 patients. Expression and incidence was evaluated by chi-square test. Association between markers was evaluated by Spearman correlation analysis.Results:1 Expression of Ki-67 in early-stage cervical cancer and CIN.Of 70 cases,18 cases of cervical cancer, 37 cases of cervical intraepithelial neoplasia and 15 cases of cervicitis , the positive expression of the Ki-67 in cervicitis , cervical intraepithelial neoplasia and cervical cancer were as below as 33.33%, 89.19% and 100.00%. The positive expression of the Ki-67 in CINI and CINII/III were as below as 85.00%, 94.12%. The positive expression in CIN and in cervix carcinoma were significantly different from that one in cervicitis (P<0.05). The intense positive expression evaluation shows significantly difference between SCC/CINII/III and cervicitis (P<0.05) The intense positive expression shows little difference between LSIL and cervicitis, as well as between CINII/III and cancer. But there was significant difference of expression between LSIL and HSIL.2 Expression of PCNA in early-stage cervical cancer and CIN.Of 70 cases, 18 cases of cervical cancer, 37 cases of cervicalintraepithelial neoplasia and 15 cases of cervicitis , the positive expression of the PCNA in cervicitis,cervical intraepithelial neoplasia and cervical cancer were as below as 66.67%, 97.30% and 100.00%. The positive expression of the PCNA in CINI and CINII/III were as below as 95.00% and 100.00%. The positive expression in CIN and in cervix carcinoma were significantly different from that one in cervicitis (P<0.05) . The intense positive expression evaluation shows significantly difference between SCC/CINII/III and cervicitis (P<0.05) The intense positive expression shows little difference between LSIL and cervicitis, as well as between CINII/III and cancer. But there was significant difference of expression between LSIL and HSIL.3 Association of Ki-67 and PCNA expressionAccording to Spearman correlation analysis, there was a positive correlation among Ki-67 and PCNA expression (rs=0.6565, P<0.01) .4 HPV detected in early-stage cervical cancer and CIN .Of 70 cases, 18 cases of cervical cancer, 37 cases of cervical intraepithelial neoplasia and 15 cases of cervicitis , the positive expression of the HPV in cervicitis,cervical intraepithelial neoplasia and cervical cancer were as below as 13.33%, 72.97% and 100.00%. The positive expression of HPV in CINI and CINII/III were as below as 30.00% and 82.35%. The positive expression in CIN and in cervix carcinoma were significantly different from that one in cervicitis (P<0.05). The incidence shows significantly difference between SCC/CINII/III and cervicitis (P<0.05)The intense positive expression shows little difference between LSIL and cervicitis, as well as between CINII/III and cancer. But there was significant difference of expression between LSIL and HSIL.Results of PCR was compared with HCII results in 33 patients , including 5 early-stage cancer, 12 HSIL , 10 LSIL and 6 cervicitis. There are coincidence between them except for 3 PCR(+)/hcII(-) results in 1 cancer and 2 LSIL cases.5 Association of HR-HPV and Ki-67 / PCNA expression.According to Spearman correlation analysis,there was a positive correlation among HPV and Ki-67 expression (rs=0.6072, P<0.05). There was also a positive correlation among HPV and PCNA expression (rs=0.7835, P<0.05).Conclusions:Up-regulation of Ki-67, PCNA expression indicate cervical dysplasia. The intense expression is significantly related to HSIL and cervical cancer. Ki-67, PCNA expression among LSIL and cervicitis is not significant, as well as among HSIL and early-stage cancer. The difference between LSIL and HSIL is significant. There was a positive correlation among Ki-67 and PCNA expression. Positive HPV results indicate potential danger of precancerous lesion, and is related to SCC significantly. There was a positive correlation among HPV and Ki-67 expression and among HPV and PCNA expression. Ki-67, PCNA could be used as markers for early diagnosis of cervical cancer together with HPV test. It could be helpful for increasing the ratio of earlier diagnosis in the field of HSIL and early-stage cervical cancer.