Expression And Prognostic Significance Of Ki-67,Geminin And H3S10ph Protein In Non Small Cell Lung Cancer

Objective：To investigate the expression of Ki-67, Geminin and H3S10ph in Nonsmall cell lung cancer and to explore the relationship between their expression andclinicopathological parameters. Meanwhile, to divide cell cycle to3stages accordingto the expression of Ki-67and Geminin, and further to study if this cell cycle divisionmuch correlates with the prognosis of patients.Methods：96cases of pathologically diagnosed Non small cell lungcarcinoma(NSCLC) and10cases of cancer-adjacent normal tissues were obtainedfrom People's hospital of Jiangxi province. The diagnosed dates were from2006to2010. By tissue microarray method, all samples were embedded into two paraffinblocks. The protein expression of Ki-67, Geminin and H3S10ph were detected on theparaffin sections by Envision two-step immunohistochemiscal method. Therelationship between the protein expression and clinicopathological parameters wasstudied and patients' prognosis was evaluated. Cell cycle was divided to3stages(stageI, II and III) according to the expression of Ki-67and Geminin.Chi-square and Fisher exact probability tests, non-parametric Spearman rankcorrelation analysis were used to analyze the relationships between theclinicopathological parameters and immunohistochemical variables. Univariatesurvival analysis and the cell cycle stage applies Kaplan-Meier method and Log-Ranktest to calculate and compare the cumulative survival rate and postoperative meansurvival time in52patients with NSCLC. COX proportional hazards regressionmodel was used for multivariate survival analysis.Results：(1) The expression rate of Ki-67, Geminin and H3S10ph in96cases NSCLCwere77.1%(74/96),67.7%(65/96)and46.9%(45/96)respectively. The positiveexpression rate of both of three in10cases tumor-adjacent normal tissues were10.0%(1/10),40.0%(4/10)and10.0%(1/10). The expression of Ki-67and H3S10ph inNSCLC were higher than in adjacent normal tissues(P<0.05).(2) In the all cases ofNSCLC, the expression of Ki-67and H3S10ph were different in various age and theexpression of Geminin was different in diverse age and age(P<0.05), but the expression of them in other clinicopathological parameters had nodifferences(P>0.05).(3) Non-parametric Spearman rank correlation analysis showedthat: there was a positive correlation with Ki-67and Geminin(r=0.239, P<0.05); anda positive correlation with Ki-67and H3S10ph(r=0.381, P<0.05), while there wereno correlations between Geminin and H3S10ph (p>0.05).(4) In follow-up data of52patients, the higher expression of Ki-67and Geminin patients have the lowercumulative survival rate(P<0.05).(5) Univariate survival analysis demonstrated that:there were significant differences in median survival time according to pathologictype, differentiation and lymph node metastasis (P<0.05). COX multivariateregression model showed that: only differentiation(RR=0.409,95%CI=0.196-0.857,P=0.018)and lymph node metastasis(RR=6.490,95%CI=1.983-21.238,P=0.002)are the independent prognostic factors influencing prognosis of NSCLC patients.(6)According to cell cycle algorithm, we divided follow-up data into three cell cycle andfound that: this staging method was different in survival time(Log rank test,P<0.05).Conclusions：(1) There was a correlation between expression of Ki-67,Geminin andH3S10ph in NSCLC and clinicopathological parameters.(2) The expression of Ki-67and H3S10ph in NSCLC were higher than in adjacent normal tissues. And threeproteins expression in NSCLC have some relationship between each other.(3) Therewere significant differences in median survival time according to pathologic type,differentiation and lymph node metastasis. Differentiation and lymph nod metastasiswere independent factors of clinical outcome in NSCLC.(4)High expression of Ki-67and Geminin was associated with poor survival.(5) It is feasible to use Ki-67andGeminin to divide cell cycle and evaluate prognosis.