A comprehensive immunohistochemical and molecular approach to the PI3K/AKT/mTOR (phosphoinositide 3-kinase/v-akt murine thymoma viral oncogene/mammalian target of rapamycin) pathway in bladder urothelial carcinoma

摘要: What's known on the subject? and What does study add? A few published studies investigating single or various PI3K/AKT/mTOR signalling components have produced inconsistent results. Moreover, PI3K regulatory subunit p85a activated p70S6K expression levels not been previously examined in urothelial carcinoma (UC). The present addresses simultaneously all key members of cascade supporting a differential implication pathway tumorigenesis. Furthermore, we propose p-4E-BP1 as potential prognostic marker UC, which might assist selection patients more likely to benefit from chemotherapy regimens based inhibition. Finally, indicates PIK3CA/AKT1 mutational status predictive for time-to-recurrence. OBJECTIVE •  To perform comprehensive simultaneous assessment phosphoinositide 3-kinase/v-akt murine thymoma viral oncogene/mammalian target rapamycin (PI3K/AKT/mTOR) along with AKT homolog 1 (AKT1) PIK3 catalytic alpha polypeptide (PIK3CA) mutations bladder (UC). •  Published information is limited looking into combinations this In particular phosphorylated (p-)p70S6 kinase (p70S6K) has tested UC. PATIENTS AND METHODS •  Paraffin-embedded transurethral resection tissue 113 UC was investigated association p85aPI3K, p-AKT, p-mTOR, p-p70S6K (eukaryotic initiation factor 4E-binding protein 1) status, well PIK3CA AKT1 p-extracellular signal-regulated 1/2 (ERK1/2), fibroblast growth receptor 3 (FGFR3), pathological features, recurrence cancer-specific survival. RESULTS •  With exception p-p70S6K, others were upregulated UCs compared normal urothelium. •  p-mTOR strongly correlated its upstream p-AKT marginally downstream p-p70S6K. p85aPI3K p-ERK1/2 also correlated. •  PIK3CA distinctly uncommon mutually exclusive, without any features. However, presence associated increased FGFR3 restricted immunonegative cases, whereas mutant cases had lower levels. •  The combined shorter recurrence-free survival univariate analysis. An inverse relationship established between immunopositivity histological grade T category, latter being marginal significance. •  p-4E-BP1 nuclear lymphovascular invasion adversely affected multivariate, but analysis. CONCLUSIONS •  PI3K/AKT/mTOR appear be differentially implicated tumorigenesis and, are unrelated status. •  Our findings independent axis inhibition. •  PIK3CA/AKT1 may place prediction time-to-recurrence.