MP54-02 COMBINED LAPAROSCOPIC RADICAL NEPHRECTOMY WITH THORACOSCOPIC THROMBECTOMY FOR RENAL CANCER WITH LEVEL 4 INFERIOR VENA CAVAL THROMBUS

INTRODUCTION AND OBJECTIVES: To date, few studies have evaluated the prognostic value of biomarkers associated with the mammalian target of rapamycin (mTOR) pathway in renal cell carcinoma (RCC); therefore, the impact of these markers on the prognosis of patients with RCC, particularly in those with non-metastatic disease, remains largely unknown. The objective of this study was to evaluate the expression of multiple molecular markers involved in mTOR signaling pathway in RCC to determine the prognostic significance of these markers following radical nephrectomy. METHODS: The expression levels of 5 markers, including PTEN, phosphorylated (p)-Akt, p-mTOR, p-p70 ribosomal S6 kinase (p70S6K), and p-4E-binding protein 1 (4E-BP1), were measured in radical nephrectomy specimens from 137 patients with non-metastatic RCC by immunohistochemical staining. These findings were analyzed according to several clinicopathological outcomes. RESULTS: During the observation period, 59 of the 137 patients (43.0%) developed disease recurrence (lung in 48, lymph node in 9, liver in 3 and bone in 2), and 1-, 3-, and 5-year recurrence-free survival rates were 80.2%, 67.9%, and 58.3%, respectively. On Univariate analysis, expression levels of p-mTOR and p-4E-BP1, in addition to the C-reactive protein (CRP) level, pathological stage, and microvascular invasion were identified as significant predictors for disease recurrence. Of these factors, the expression of p-4E-BP1, CRP level and pathological T stage appeared to be independently related to recurrence-free survival on multivariate analysis. Moreover, significant differences were observed in recurrence-free survival according to the positive numbers of these three independent factors; that is, disease recurrence developed in 5 of 42 patients negative for any risk factor (11.9%), 23 of 50 patients positive for a single risk factor (46.0%), and 31 of 45 patients positive for two or three risk factors (68.8%). CONCLUSIONS: These findings suggest that the combined evaluation of the expression levels of potential markers in the mTOR signaling pathway, particularly p-4E-BP1, in RCC specimens with conventional prognostic parameters would contribute to the accurate prediction of disease recurrence following radical nephrectomy for nonmetastatic RCC. However, it may be required to draw a definitive conclusion on this issue to perform a prospective study targeting additional molecules mediating the signaling cascade associated with the mTOR signaling pathway.