KRAS, BRAF, PİK3CA mutation analysis in bladder infiltrative urothelial carcinoma

AIM: Bladder cancer is the most common cancer of the genitourinary system after prostate and 7th most common cancer among the cancers in the world with obvious male predominance. Urothelial tumors are divided into two major groups according to their molecular pathogenesis: Non-muscle invasive (pT0, pT1) and infiltrating urothelial carcinomas (IUC) (pT2-pT4). Since, IUC tend to progress and metastasize, more aggressive treatment (cystectomy, chemotherapy) is applied. Therefore, the discovery of molecular pathways to develop new treatment methods, especially in invasive bladder cancers is important. Based on the new discoveries at bladder cancers, we aimed to define mutations seen on receptor tyrosine kinase pathway (KRAS, BRAF, PIK3CA). MATERIAL AND METHOD: A total of 24 cases of IUC from the archive of Düzce University School of Medicine, Department of Pathology&Cytology were included. IUC cases were divided into two categories according to whether there is divergent differentiation or not. Appropriate tumor area was detected on microscopic examination and macro-dissected from the paraffin-embedded samples for the mutational analysis. Respectively, DNA extraction and PCR amplification was done. PCR products were placed in RANDOX device biochip sequences and KRAS, PIK3CA and BRAF mutation analysis was performed. Results of the analysis were compared with the clinical, demographic and histopathological findings. Survival rates were evaluated according to the mutations and chemotherapy regimens. RESULTS: The mean age at diagnosis of IUC cases was 70,2 and male / female ratio was 11/1. Fourteen patient had received chemotherapy including mostly gemsitabin+sisplatin regimens. Histopathological examination revealed in-situ component (n:8), necrosis (n:13), lymphovascular invasion (n:12) and perineural invasion (n:10). Most of the cases were diagnosed at stage 2 (79,1%). KRAS, PIK3CA, BRAF mutations were detected in 33,3%, 12,5%, 8,3% of cases, respectively. While several mutations were present in cases with glandular, sarcomatoid and squamous differentiation, there was no mutation in cases with micropapillary and clear cell differentiation. No statistically significant results could be obtained in the comparison of histopathologic properties and mutation analysis. No difference was seen between the survival rates of the cases when compared according to their analysis done in this study (KRAS, BRAF, PIK3CA). DISCUSSION: The determination of the molecular characters of tumors is a guide in the creation of targeted treatment algorithms and in choosing the appropriate patient. The receptor tyrosine kinase pathway is one of the most frequently mutated pathways in tumors. Conclusion: Studies with larger series are needed to find out the mutation profiles that may guide the treatment of patients with bladder cancer. Also, their impact to prognosis need to be investigated in larger series.