The Significations Of Ki-67,PR,P53 Expression In Luminal Breast Cancer

Objective(1)To explore the role of Ki-67 and PR in Luminal/HER2-negative breast cancer classification.(2)To investigate the correlations between P53 expression and clinicopathologic factors,prognosis of Luminal breast cancer.Methods(1)From January 2009 to December 2013,a total 581 patients with invasive,Luminal breast cancer were included in Shanghai First People’s Hospital Affiliated to Shanghai Jiao Tong University.The median follow-up time was 38months(range:6-82 months),Ki-67 Label index and PR expression were measured by immunohistochemistry.Clinicopathologic features data was compared using c~2-test,Survival analysis was using Kaplan-Meier method and comparations using Log-rank test,multiple factors analysis was using COX proportional hazards regression model.Classification of Luminal Breast cancers:(1)Luminal/HER2-negative group;Luminal/HER2-positive group;Classification of Luminal/HER2-negative Breast cancers:(2)By Ki-67 status:Luminal A(HER2negative;Ki-67<14%);Luminal B(HER2 negative;Ki-67≥14%);(3)By PR status:Luminal A(HER2 negative;PR≥1%);Luminal B(HER2 negative;PR<1%);(4)By Ki-67 and PR status:Luminal A(HER2 negative/PR≥1%/Ki-67<14%);Luminal B(HER2 negative;Ki-67≥14%and/or PR<1%).Difference was statistically significant when P-value was less than 0.05.(2)From January 2009 to December 2012,a total 283 patients with invasive,Luminal breast cancer were included in Shanghai First People’s Hospital Affiliated to Shanghai Jiao Tong University.The median follow-up time was 39months(range:3-80 months),p53 expression was assayed by IHC.Kaplan-Meier curves were applied to estimate RFS and OS,Cox’s proportional hazards model to identify prognostic variables.Results(1)Comparisons of clinicopathologic factors:Classification(1)was associated significantly with lymph node metastasis(LMN,c~2=9.228,P=0.010),Pathological type(c~2=8.320,P=0.016),histological grade(c~2=21.454,P=0.000),and relapse(c~2=7.448,P=0.006);Classification(3)was associated significantly with Age(c~2=5.066,P=0.024),and relapse(c~2=4.478,P=0.034);Classification(2)(4)were associated significantly with LNM(c~2=18.652,P=0.000;c~2=11.413,P=0.003),histological grade(c~2=61.205,P=0.000;c~2=43.482,P=0.000),tumor size(c~2=19.219,P=0.000;c~2=12.039,P=0.002);TNM stage(c~2=19.622,P=0.000;c~2=19.622,P=0.000)and relapse(c~2=8.180,P=0.004;c~2=13.731,P=0.000).Prognostic analysis:Classification(1)c~2=9.403,P=0.002;(2)c~2=10.926,P=0.001;(3)c~2=4.366,P=0.037;(4)c~2=16.855,P=0.000,all differences were statistically significant.In multivariate analysis for Luminal/HER2-negative patients:LNM(OR=2.275,P=0.000),histological grade,Ki-67(OR=1.800,P=0.041)and PR(OR=0.416,P=0.006)were independent prognostic factors for RFS.(2)P53 overexpression rate was higher in Lymph node metastasis(LNM)breast cancer than Lymph node negative breast cancer(χ~2=15.881,P=0.000),grade III breast cancer than in grade I and II breast cancer(χ~2=8.132,P=0.043),larger tumor size cancer than small size cancer(χ~2=6.285,P=0.043),Ki-67high expression cancer than Ki-67 low expression cancer(χ~2=9.092,P=0.003),all differences were statistically significant.In all the patients,the 5-year RFS for P53-overexpression group and P53-negative group were 93.1%and 83.4%(χ~2=12.609,P=0.000384)respectively.While the 5-year OS were 93.4%and 84.4%(χ~2=4.153,P=0.042),respectively.In subgroup analyses:the 5-year RFS for P53-overexpression group and P53-negative group were 97.5%and 77.4%(χ~2=7.650,P=0.006)in lymph node negative patients.In multivariate analysis,LNM(HR=2.639,95%CI:1.761-3.955,χ~2=22.095,P=0.000)and P53 overexpression(HR=2.381,95%CI:1.103-5.141,χ~2=4.880,P=0.027)were independent prognostic factors for RFS,LNM(HR=3.451,95%CI:1.891-6.297,χ~2=16.290,P=0.000)and higher histological grade(HR=2.806,95%CI:1.091-7.219,χ~2=4.582,P=0.032)were independent prognostic factors for OS.Conclusions(1)Ki-67 and PR expression were significant prognostic factors in Luminal/HER2-negative breast cancers,classification according to Ki-67 was correlative with various clinical outcomes.Classification by Ki-67 and PR may improve prognostic prediction power and the correlations between subtypes and clinicopathologic factors.(2)P53 overexpression was associated with poorer prognostic factors and showed worse prognosis,detection of P53 in Luminal breast cancer patients with negative lymph node was more clinically significant.