MP76-08 LEYDIG CELL TUMOR OF THE TESTIS: PATHOLOGICAL CHARACTERISTICS AND TREATMENT PATTERNS FROM THE NATIONAL CANCER DATABASE
The Journal of urology/The journal of urology(2020)
摘要
primary cancer from treatment-naïve patients with PSCC was used for preparation of the tissue microarray (TMA) blocks. Immunohistochemical staining was performed with antibodies against panakt, pakt, mTOR, pmTOR, pS6, pPRAS, p4epb1 and pp70S6K. Protein expression was correlated with clinical and histological tumor characteristics as well as overall (OS), disease-specific (DSS) and recurrence-free survival (RFS). Protein expression profiles of selected proteins og the mTOR/akt signaling pathway was investigated in treatment-naïve as well as cisplatin-resistant PSCC cell lines. Statistical analysis was performed with R software. RESULTS: 79 patients with PSCC were included, whereas median age was 67 yrs. 22.8% of tumors were high-grade and 25.3% HPV-positive with oncogenic types 16 and 59. Median follow-up was 20.7 mts. Expression of akt as well as pPRAS was directly, and that of mTOR and pmTOR inversely associated with grading. Overexpression of akt was an independent predictor of DSS and OS (HR: 8.0 and 4.6, respectively), whereas upregulation of mTOR was independently associated with DSS (HR: 6.5). In general, cellular concentration of akt was higher in cisplatin-resistant cells as compared to the naïve ones. Treating cells with cisplatin induced downregulation of akt in the naïve as well as its upregulation and activation in resistant cells. CONCLUSIONS: A number of protein candidates of the mTOR/ akt signaling pathway demonstrate association with histological and survival parameters of patients with PSCC, whereas akt appears to be the most promising one. This is further corroborated by cellular experiments. Further studies focusing on these proteins as marker and target structures for potential therapeutic intention are warranted.
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