| Summary: | 碩士 === 國立臺北科技大學 === 生化與生醫工程研究所 === 105 === The PI3K/Akt pathway is considerated to be essential for various cellular processes including cell growth, survival, cell motility, angiogenesis and cell metabolism. Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene and presents a negative regulator of the PI3K/Akt pathway by dephosphorylation of PIP3 to prevent Akt hyperactivation. Loss of PTEN expression and hyperactivation of Akt can result in tumorigenesis. Previous studies indicated that PTEN gene deletions were observed in early bladder cancer and upper tract urothelial carcinoma (UTUC). Other studies showed PTEN protein absence and pAkt protein expression in bladder cancer and non-small-cell lung carcinoma. We aim to evaluate the expression status and prognostic value of PTEN and PI3K/Akt pathway in UTUC. Archival formalin-fixed paraffin-embedded (FFPE) tissues from 65 UTUCs were performed by immunohistochemistry for PTEN, pAktS473 and pAktT308. Expression of each protein were compared with clinicopathologic parameters. PTEN, pAktS473 and pAktT308 protein expression were higher in adjacent normal tissues than tumor tissues. Cytoplasmic PTEN protein low expression was higher in high stage compared with low stage; nuclear and cytoplasmic pAktT308 protein low expression were higher in high grade compared to low grade. PTEN gene alternation was not associated with PTEN, pAktS473 and pAktT308 protein. In univariate analysis and multivariable analysis, cytoplasmic PTEN protein low expression (HR = 3.14, 3.29; P = 0.016, 0.017), cytoplasmic pAktS473 protein high expression (HR = 2.71, 2.64; P = 0.019, 0.027), metastatic (HR = 3.55, 2.73; P = 0.003, 0.031) had poor prognosis, however, lower pT stage was only significant in multivariable analysis (HR = 3.48, P = 0.01). Kaplan-Meier survival analysis showed that high tumor grade, metastatic, cytoplasmic PTEN (-)/ pAktS473(+) had poor survival (P - value were 0.006, 0.001 and <0.001, respectively). In conclusion, our findings implicate that PTEN, pAktS473 and pAktT308 protein appear to be an important indenpendent prognostic factor in UTUC patients.
|
|---|
