| Objective:This study was to investigate the expression of Ki-67 proliferation index in newly diagnosed multiple myeloma and its relationship with MM risk stratification and clinical prognosis.At the same time,to explore the different Ki-67 expression levels in patients' treatment options.Methods:A total of 119 MM patients who were newly diagnosed in our center from January 2016 to December 2017 were enrolled.The diagnostic criteria for MM refer to the"China MM Guidelines for the Treatment of 2015 Revision" and the IMWG(International Myeloma Diagnosis and Treatment Guide).Diagnose based on.The follow-up deadline was December 30,2018,with a median follow-up of 24 months(range 12-36 months),and 4 of 119 patients were lost to follow-up(3.3%lost).First bone marrow sample sectioning.The pathological specimens of patients with bone marrow biopsy were detected by immunohistochemical technique.The paraffin bone marrow cuts were dewaxed to hydration treatment,the endogenous enzyme was inactivated with 3%hydrogen peroxide(H2O2),and the antigen was repaired with ethylenediaminetetraacetic acid(EDTA)antigen repair solution and placed in PBS buffer.Soak in the liquid for 10 minutes.Primary antibody and secondary antibody were added dropwise.The primary antibody was mouse anti-human Ki-67 monoclonal antibody,DAB was stained,and hematoxylin was counterstained for 30 s.Bone marrow biopsy immunohistochemical markers including CD138,CD38,kappa,lamda,MUM1,CD19,CD45,CD56,CD117,CyclinDl,bcl2,bcl6,c-myc,CD20,Ki-67,simultaneously labeled with Congo red and crystal violet With or without amyloidosis.The number of Ki-67 staining positive cells in myeloma cells per field was determined by OLYMPUS BX51 microscopy.The positive standard was brown stained granules in the nucleus or cytoplasm.At least 500 cells were counted in the positive region,and the Ki-67 proliferation index of the bone marrow biopsy immunohistochemistry was calculated according to the established formula,that is,the number of positive cells/the number of cells measured.The expression of Ki-67 index in MM was analyzed by spss25 statistical software.Results:1.Clinical characteristics of 119 newly diagnosed MM patients:73 males and 46 females with a median age of 60 years.Immunological classification can be divided into 6 categories according to the secretion of immunoglobulin:63 cases(52.9%)of IgG type,25 cases(21%)of IgA type,10 cases(8.4%)of k light chain type,? light chain type 12 For example(10.1%),6 cases(5%)of IgD type,3 cases(2.5%)of other types(1 case of IgM type,1 case of IgE type,1 case of oligosecretion type).There were 116 cases of DS staging due to imperfect initial diagnosis data,including 2 cases(1.7%)in stage ?,6 cases(5.2%)in stage ?,and 108 cases(93.1%)in stage ?.There were 115 cases of feasible ISS stage,including 34 cases(29.6%)in stage ?,35 cases(30.4%)in stage ?,and 46 cases(40%)in stage ?.There were 109 cases of feasible R-ISS staging,including 27 cases(24.8%)in stage ?,60 cases(55%)in stage ?,and 22 cases(20.2%)in stage ?.There were 69 cases of extramedullary plasma cell tumors,including 7 cases of extramedullary plasma cell tumors(10.1%)and 62 cases of extramedullary plasmacytoma(89.9%).There were 111 patients who underwent chromosomal examination,including 83 normal karyotypes(74.8%)and 28 complex karyotypes(25.2%).86 patients were tested for cytogenetic changes by fish,and 23 patients(26.7%)were at high risk.),63 patients(73.3%)were at risk.Of the 117 patients who were assessed for bone destruction,110(94%)had bone destruction and 7(6%)had no bone destruction.2.The expression level of Ki-67 in 119 patients with MM was0%-70%,and the Ki-67 cut-off value was 17.5%.The OS was different(P=0.009).Correlation analysis showed that high expression of Ki-67 was associated with high LDH(P=0.022)and associated with extramedullary plasmacytoma(P=0.001).The expression of Ki-67 index in R-ISS phase ?was significantly higher than that in patients with ? and ?(P=0.036).The Plt and ALB of patients with stage R-ISS were significantly lower than those of stage ? and ?(P=0.001 and 0.008 respectively),while patients with stage R-ISS LDH,blood Cr,serum Ca,?2-MG,complex Chromosomes and high-risk cytogenetics(fish detection)were higher than those in stage ? and ? patients(P<0.05).3.Analysis of therapeutic efficacy in patients with different Ki-67 expression levels:116 patients with statistically relevant first-line chemotherapy,of which 99(85.3%)were based on bortezomib and 9 were based on lenalidomide.For example(7.8%),there were 8 cases(6.9%)based on thalidomide.A total of 118 patients participated in the statistical history of transplantation,of which 56(47.5%)received stem cell transplantation during first-line treatment and 62(52.5%)without transplantation.There was no difference in the history of first-line chemotherapy and the history of transplantation between Ki-67?17.5%and Ki-67>17.5%(P=0.206;P=0.244).The overall effective ORR(partial remission and above)between the Ki-67 high and low groups was 69.9%and 90%,respectively,with statistical difference(P=0.009).In the low expression of the Ki-67 group,the proportion of patients who achieved CR was significantly higher(37%vs.13.3%)(P=0.016).4.The guiding significance of different Ki-67 expression levels in the selection of treatment options:Ki-67>17.5%expression level,comparing the effects of bortezomib,lenalidomide and thalidomide on OS There was no difference(P values were 0.768).On the Ki-67?17.5%expression level,there was no difference in the effects of bortezomib,lenalidomide and thalidomide on OS(P values were 0.217).5.Analysis of survival and influencing factors in 119 patients with MM:At the follow-up,the OS was 1-35 months and the median OS was not reached.Using a 17.5%cut point,there was a difference in OS between the high Ki-67 group and the low Ki-67 group(P=0.009),and the cutoff value of Ki-67>17.5%patients had a cumulative survival rate lower than?17.5%.At the same time,other influencing factors analysis showed:LDH,serum Ca,blood ? 2-MG,Cr,R-ISS staging,cytogenetics and OS were associated(P<0.05).Multivariate analysis showed that patients who achieved PR or higher survived longer,and patients with MR,PD,and SD had shorter OS,and the disease remission status after induction was related to the overall survival of the disease(P=0.002).Conclusion:Proliferation-associated antigen Ki-67>17.5%as a MM hyperproliferative stratification standard,is one of the poor prognostic indicators of MM,suggesting that the overall survival time of patients is shortened.High expression of Ki-67 is associated with high LDH and extramedullary tumorigenesis.Ki-67 is expressed more in R-ISS stage III patients.Patients with high Ki-67 expression had poor remission after first-line chemotherapy.The stratified design of selective treatment regimens for different proliferation activities of MM is the next step in clinical research. |
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