The Value Of P16, Ki67 And CK7 In Predicting The Outcome Of Low-grade Cervical Intraepithelial Neoplasia(CIN11)

Objective:Cervical intraepithelial neoplasia is cervical precancerous lesions. There exists some problems in intervention clinical practice, the prominent problem is CIN treatment which is chaotic, the excessive treatment is relatively common. There is a “better lefe not right”phenomenon especially in the diagnosis and treatment of CIN1. The adverse consequences caused by infertility, miscarriage, premature birth, cervical incompetence and more mesarean section rate has been increased year by year, especially for young women with desire to procreate leading to great physical and psychological health threat.This issue has already caused the extensive concern of scholars at home and abroad.Looking for the influence factors of CIN1 development, the accurate and objective evaluation of CIN1 before treatment, and constructing the early warning model for the development of CIN1 is an important direction of CIN1 research at this stage. At home and abroad, many studies have confirmed that P16, Ki67, CK7 immune factors are closely related with the occurrence and development of cervical lesions and its prognosis.So the purpose of this study are: 1. To study whether the expression of P16, Ki67, CK7 three immunohistochemistry factors in different prognosis CIN1 tissues were different; 2.To calculate the sensitivity, specificity, positive predictive value and negative predictive value of P16, Ki67 and CK7 in the prognosis of CIN1, and to evaluate the diagnostic value of the three indicators of immunohistochemistry in detection of six months after the lesion CIN1 not regressing; 3. To investigate the factors affecting the prognosis of CIN1 lesions.Methods:From June 2014 to June 2015 in" Public welfare project of health industry in Shanxi Province” for screening of cervical lesions in diagnosis of CIN1, half a year without therapeutic intervention, at the 6th months, doing another colposcopic biopsy, and according to the follow-up of the disease inspection results, the first diagnosis of CIN1 were divided into promotion group, sustained group and subsidise group. There are 16 patients in promotion group, 57 patients sustained group, randomly selected 25 patients from the subsidise group. Collect the paraffin, HE staining and related clinical data of the98 cases. In order to avoid the subjective factors of the existence of the pathological physicians, at least three Pathology doctor read pathological section to verify diagnosis once again. The staining of P16, Ki67 and CK7 in paraffin sections was detected by immunohistochemical staining SP method, and then the data were analyzed statistically.Results:1. The age of progression group, maintenance group and regression group respectively were: 40.06±8.67、46.69±8.59、42.80±10.52. The age of progression group was less than the maintenance group’s, and the difference was statistically significant(t=-2.641,P=0.010). Menopause in the three groups was different, and the difference was statistically significant(P < 0.05). There were 15 non-menopause patients in progression group, and 35 cases in maintenance group, the difference was statistically significant( c 2=6.057, P = 0.014). TCT results, HPV infection, menstrual pattern, condom use,sexual partner smoking in the three groups were not statistically significant difference, P values were greater than 0.05.2. In progression, maintenance and regression group, P16 positive expression rates were 75.0%, 29.8%, 44.0%, and CK7 positive expression rates were 68.8% and40.4%, 20.0%; Ki67 negative expression rates were: 6.2%, 10.5%, 20.0%, "1 +" e xpression rates were: 50.8%, 75.4%, 76.0%, "2 + " expression rates were: 31.2%,8.8%, 4.0%, the "3 + " expression rate was 12.5%, 5.3%, 0%. P16 expression was higher in progression group than maintenance group, and the difference was s tatistically significant(c2=10.648, P=0.001). The CK7 expression was higher in pr ogression group than maintenance group, and the difference was statistically signif icant(c2=4.049, P=0.044); The progression group’s Ki67 expression positive rate was higher than that in regression group, the difference was statistically significan t(c2=9.259, P = 0.014). The same to positive rate of CK7 expression(c2=9.744,P=0.002). There was no significant difference between the maintenance group and regression group, and the P value was greater than 0.05.3. When using the three immune marker- p16, Ki67 and CK7 predicted CIN1 not maintenance after six months, the sensitivity were 0.397, 0.205, 0.466, specificity respectively were 0.560, 0.960, 0.800,the positive predictive value were 72.50%, 76.74% and 87.17%, the negative predictive value were24.10%, 41.70%, 33.90%. The sensitivity and positive predictive value of CK7 were the highest. ROC curve analysis results of P16, Ki67 and CK7: CK7 curve area was 0.633(95% CI 0.495~0.740), the difference is statistically significant(P = 0.048). CK7 positive expression of detection of six months after the lesion CIN1 does not maintenance, has certain diagnostic value.4, CIN1 after six months of disease progression and the disease continues to be classified as a patient group, patients with lesions subsided for the non patient group. Statistics found that CK7 is still related to the disease of CIN1 after six months( ? 2=5.489,P=0.019). And age, P16 and Ki67, HPV infection, regular menstruation, menopause,condoms, contraceptive, a partner who smokes, the age of menarche has nothing to do with half a year of CIN1 after the illness(?2=0.141, P = 0.707; ?2=6.446, P = 0.092;? 2=0.065, P=0.799; ? 2=1.882, P = 0.170; ? 2=0.108, P=0.743; ? 2= 0.118, P=0.731;?2=2.832, P = 0.092; ?2=5.232, P = 0.384; ?2=-1.051, P = 0.296). Introducing the factor in the single factor analysis(CK7 positive) and factors according to the reports about CIN1 disease and prognostic into non conditional Logistics regression model for multivariate analysis. The positive expression of Ki67(OR=9.609, 95%CI:1.121~81.344),the positive expression of CK7(OR=8.900, 95% CI:2.102~37.681), aged 41-50 years old(41-45 years old OR=29.188. 95%CI:1.583~538.092; 46-50 year old OR=27.074,95%CI:1.559~470.070), menopause(OR=19.852, 95%CI:1.381285.343) have been introduced into the regression model, and the positive expression of P16 and HPV infection, regular menstruation, condom using, husband smoking, less than 40 years of age, the age of menarche were excluded.Conclusions:1. The three immunohistochemical factors of P16,Ki6,CK7 have different expression quantity in different prognosis CIN1 organizations: lesions progress group of positive P16 expression rate is higher than lesions continued group;lesions progress group Ki67 above “1”expression rate is higher than lingering lesion group; lesions progress group of positive CK7 expression rate is higher than disease group and lingering lesion group;2. The positive CK7 has a highest sensitivity and positive predictive value in CIN1 prognosis, it also has a vast area in POS curve, which has a great diagnostic value in CIN1 lingering lesions which has been detected for half a year;3. The women who are 41-50 years old or who are already menopause or who are with positive expression of Ki67 and CK7, might be the risk factors of CIN1 patients after six months still sickness.