Clinical Prognostic Correlation Of Molecular Subtypes In Muscular Invasive Bladder Cancer

OBJECTIVE: To explore relationships between molecular types of muscle invasive bladder cancer(MIBC)based on Immunohistochemistry(IHC)and clinicopathologic features while prognosis of patients;To provide theoretical basis for the individualized treatment of MIBC.2.Analyze the expression of p53 and human epidermal growth factor receptor(HER2)in MIBC and the prognosis of different expression states,and evaluate the correlation between the above two markers and different types.Molecular subtypes related to p53 and HER2 were constructed by IHC,so as to provide guidance and suggestions for clinical selection of the most appropriate adjuvant therapy.METHODS: 1.A total of 100 patients diagnosed with MIBC by pathology and hospitalized in the Department of Urology,Hainan Hospital Affiliated to Hainan Medical University(Hainan Provincial People’s Hospital)from June 2017 to June2022 were collected,and the histological type was all bladder uroepithelial carcinoma.The clinical data of 100 patients with MIBC were retrospectively analyzed,and the survival status of the patients was followed up by telephone inquiry and outpatient return visit.The expression levels of CK20 and CK5/6 in MIBC pathological specimens were detected by IHC,and MIBC was divided into luminal type(CK20+,CK5/6-),basal type(CK20-,CK5/6+),double positive type(CK20+,CK5/6+)and double negative type(CK20-,CK5/6-).To explore the relationship between different molecular subtypes and clinicopathologic features and prognosis of patients.2.The protein expression levels of p53 and HER2 were detected by IHC to analyze the prognosis of patients,evaluate the correlation between the above two markers and CK20 and CK5/6 and their expressions in different molecular subtypes,construct molecular subtypes related to p53 and HER2,and explore their prognosis and optimal treatment plan.3.SPSS 26.0 software was used for statistical analysis and R language software survival package was used for Kaplan-Meier analysis and mapping.RESULTS: 1.A total of 100 patients with MIBC were enrolled in this study,of which 43(43%)were luminal type,34(34%)were basal type,13(13%)were double positive type,and 10(10%)were double negative type,among which luminal type accounted for the highest proportion.2.There were statistically significant differences in pathological staging and distant metastasis among different molecular subtypes(P < 0.05).Patients with luminal type and doubl positive type were mostly at T2 stage,and there were few distant metastases.Basal type and double negative type patients mostly had T4 stage,and were more likely to develop distant metastasis.3.Kaplan-Meier analysis showed that the OS and DFS of patients with lumen type and double positive type were higher than those of basal type and double negative type,and the difference was statistically significant(P<0.05).4.Univariate Cox analysis showed that pathological stage,distant metastasis and molecular subtypes were potential risk factors affecting the prognosis of patients(P<0.05),while multivariate Cox analysis showed that pathological stage and molecular subtypes were independent risk factors affecting the prognosis of patients(P<0.05).5.The expression of p53 and HER2 was detected by IHC.There were 22 patients(22%)with positive expression of p53 and 78 patients(78%)with negative expression.There were 51 patients with positive expression of HER2(51%)and 49 patients with negative expression of HER2(49%).Kaplan-Meier analysis showed that the OS and DFS of patients with negative expression of p53 and HER2 were higher than those of patients with positive expression,and the difference was statistically significant(P<0.05).Both p53 and HER2 can be used as molecular markers to evaluate the prognosis of MIBC.6.There was no correlation between p53 expression and CK20 and CK5/6 expression(r=0.179,r=-0.113,P>0.05).HER2 expression was positively correlated with CK20 expression(r=0.380,P<0.05),and negatively correlated with CK5/6 expression(r=-0.199,P<0.05).7.There was no significant difference in the expression of p53 among the four molecular subtypes(P>0.05);HER2 was significantly different among the four molecular subtypes(P<0.05),and HER2 was highly expressed in luminal tumors.8.As p53 is not correlated with CK20 and CK5/6,and its expression is not different in each subtype,it cannot be classified temporarily.9.A new subtype related to HER2 was constructed and named HER2 type(CK20+,CK5/6-,HER2 positive),which belongs to luminal type,and the survival situation of patients with HER2 type was analyzed.Kaplan-Meier analysis showed that there was no significant difference in OS and DFS between HER2 and luminal non-HER2 patients(P>0.05).10.A case of HER2 type metastatic urothelial carcinoma undergoing surgical treatment after neoadjuvant therapy was reported,and the best adjuvant therapy plan for HER2 type MIBC was discussed.CONCLUSION: 1.Molecular subtypes of MIBC based on immunohistochemistry can be divided into four types: luminal type,basal type,double positive type and double negative type.2.The molecular subtypes of MIBC were significantly correlated with the clinical stage and prognosis of patients.Patients with luminal type and double positive type were mostly in the T2 stage,less distant metastasis occurred,and the prognosis was better.Patients with basal type and double negative type mostly have T4 stage,which is more prone to distant metastasis and poor prognosis.The characteristics of different molecular subtypes can help clinicians choose the appropriate treatment and evaluate the prognosis.3.p53 can be used as a prognostic indicator for MIBC,but has no correlation with the molecular subtypes of MIBC.4.HER2 can be used as an indicator to evaluate the prognosis of MIBC,and it is correlated with luminal type.HER2 combined with molecular subtypes can better guide the individualized precision therapy of MIBC.